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415 Cards in this Set
- Front
- Back
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TRH from hypothalamus simulates what?
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TSH from ant pituary which then acts on thryoid
Prolactin from ant pituitary which then acts on breasts |
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TSH has what affect on thyroid?
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stimules thryoid to secrete thyroxineT4, triiodothyronine T3
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prolactin has what affect on breasts?
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stimulate breast development and milk production and in males facilitates reproductive fxn
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Dopamine from hypothalamus inhibits what?
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inhibits prolactin rlease from ant pituitary
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CRH from hypothalamus stimulateas waht?
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ACTH release from ant pituiatary to act on adrenal cortex to secrete cortisol
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vasopressin acts on what ant pituitary hormone?
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ACTH which then tells adrenal cortex to secrete cortisol
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what is the affect of SS release from hypothalmus?
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inhibits TSH from ant pituitary
inhibits GH from ant pituiatary |
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what is the affect of GHRH from hypothalmus?
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stimulates GH release from ant pituitary
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what is the affect of GH?
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acts on liver cells to secrete IGF-1
stimulates protien syn influences carb and lipid metabolism |
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what is the affect of GnRH from hypothalamus?
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stimulates release of LH and FSH form ant pituiatary
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what is the blood supply of the ant lobe of pituitary?
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ICA gives off superior hypophyseal artery
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what is the blood supply of the post lobe of pituitary?
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ICA gives off inferior hypophyseal artery
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what exists b/n the ant and post lobes of pituitary?
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hypophysial-portal vascular connection in the pituitary stalk
vein to vein portal system linking fenestrated capillaries |
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how do hormones from hypothalamus travel to ant pituitary?
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hypothalamic hormones travel to the anterior lobe by way of a special capillary system, called the hypothalamic-hypophyseal portal system.
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how do hormones from hypothalamus reach post pituitary?
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Hormones are made in nerve cell bodies positioned in the hypothalamus, and these hormones are then transported down the nerve cell's axons to the posterior pituitary. Hypothalamic neurons fire such hormones, releasing them into the capillaries of the pituitary gland.
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what are the nuclei associated with the post pituitary?
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paraventricular and supraoptic nuclei secrete oxytocin and vasopressin directly into capillaries in the posterior lobe
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what are the 6 hormones produed by ant pituitary?
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FLAT PiG
produces six peptide hormones: prolactin, growth hormone (GH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). |
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fxn of osteoblasts?
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bone forming cells
secrete bone matrix on which Ca and PO4 precipitate |
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what is an osteoclast? derived from?
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large multinucleated cell derived from monocytes
fxn resorb bone |
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what hormone inhibits bone formation?
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cortisol
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what are the 3 regulators of Ca?
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PTH
Calcitonin Vitamin D3 1,25 dihydroxy |
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what hormone stimulates Vit D synthesis?
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PTH
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action of 1 aplha hydroxylase?
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activates Vit D
PTH stimulates 1 alpha hydroxylase |
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action of phosphate on 1 alpha hydroxylase?
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decreases
decresaed levels of PO4 increase 1 alpha hydroxylase |
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main action of activated Vit D?
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stimulate absorption of Ca form liver by stimulating prod of calcium binding protein
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what cells produce PTH?
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chief cells of parathyroid
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when is PTH secrted
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inversely related to serum Ca concentration
secreted when Ca is low in plasma |
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what is the overall action of PTH?
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increase plasma Ca levels
decrease plasma phosphate |
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action of PTH on bone? kidney?
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directly affects bone by increasing Ca resorption
reabsorption of Ca in DCT and inhibit reabsorption of PO4 |
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what hormone causes a decrease in plasma Ca?
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calcitonin
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what cells synthesize and secrete calcitonin
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parafollicular cells of thyroid
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target cell for calcitonin?
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osteoclast causing inactivation
inhibit bone resorption |
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steroid hormones are derived from the modification of what?
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choloesterol
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where is most of the cholesterol used for steroid hormone syn obtained from?
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circulating LDL
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how is cholesterol obtained from LDL?
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circulating LDL binds to PM LDL R and is internalized by Rmediated endocytosis into a lysosome. In the lysososme it is digested and cholesterol is released into the cell. The cholesterol is then used for steroid H syn or stored in the form of CEs w/n lipid droplets by the action of cholsterol esterase
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how is cholesterol converted into the CE storage form? how are CE mobilized back into cholesterol?
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by acyl CoA: cholesterol acyltransferase
mobilized by cholesterol esterase |
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where does steroid hormone syn occur?
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mt.
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what enzyme is involved in the first step of steroid hormone syn?
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StAR: steroidogenic acute regulatory protein located in inner mt mem.
moves cholesterol from outer mem to inner mt mem |
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how is StAR activated and newly synthesized?
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by cAMP dependent mech that activates PKA
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what is the rate limiting step in steroid H syn? where does it occur?
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inner mt membrane
cholesterol converted to pregnonolone |
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what is pregnonolone/
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precursor for all adrenal, gonadal, and placental steroids
syn occurs when cell is stimulated |
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cholesterol esterase is stimulated by?
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PKA
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in terms of steroid H syn, when cAMP increases, PKA is p-lated increasing the syn of what impt protein?
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StAR which then promotes the flow of cholesterol into mt
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the rate of steroid H syn depends on what
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rate of release
there are no special mxns for storing steroid H's (steroidogenic cells DO NOT contain stored hormone) |
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steroid H are not very soluble in waht solns? how do we solve this problem?
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aqueous solns
steroid H are bound to binding proteins |
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the 3 main specific steroid H binding proteins are?
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sex hormone binding globulin (SHBG) binds androgens and estrogens
Corticosteroid binding globulin (CBG)-binds cortisol and progersterone Vitamin D binding globulin (DBG) |
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a fraction of steroid H pool binds non-specifically and with low affinity to what?
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albumin
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what is impt about the free fraction of steroid Hormone?
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can readily bind to R's in target tissues and induce a physiological response
readily pass through PM |
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besides the free fraction of steroid H, which other bound steroid H is also readily available to target tissues?
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that bound non specifically to albumin b/c of the weak binding
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why are steroid H converted to inactive metabolites?
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b/c humans do not have enzymes that can degrade the steroid nucleus
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what is the prinicipal site of steroid H inactivation?
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liver
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after steroid H are inactivated in liver, what are they conjugated with?
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glucoronic acid or sulfate to increase the solubility of steroid and decrease affinity of steroid hormone for binding proteins thus facilitating the clearance of inactivated steroid H
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the conjugated inactivated steroid H are excrted prinicipally by what?
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kidneys
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what happens to the steroid H that are not inactivated?
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they are converted to more active metabolite or metabolit with different action in peripheral tissue (2ndary organ)
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what is characteristic of steroid H receptors?
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nuclear R's
ligand activated TF nuclear locatialization signal |
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when the steroid H binding site is unoccupied, the steroid H R's form large complexes with what?
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heat shock proteins
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what happens when steroid H binds steroid H R?
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the R dissociates from hsp's and forms HOMOdimer with another occupied R for same H
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when do steroid H R's bind DNA? when they do bind to DNA, what is the target?
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only when H is bound to appropriate binding sites on R
when they are hormone occupied they bind to target genes by means of HRE that is located in regulatory region of target gene |
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what is recruited by steroid H bound dimers that bind HRE?
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this is H depdent activation of gene trascription
coactivator proteins are recruited that have HAT activity to lessen interaction iwth DNA and histones promote DNA unwinding |
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waht is the action of steroid H R antageonist?
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incduces conf change in the R that prvents coactivators from binding and favors corepressors
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zona glomerulosa secretes?
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mineralcorticoids: aldosterone
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what is the principal minearlcorticoid in humans?
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aldosterone
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what is the primary regulator of aldosterone S?
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renin-angiotensin system
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what makes up adrenal cortex?
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zona glomerulosa, fasiculata, reticularis
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what is released from the JG cells in response to decreased arterial BP, sympathetics, and decrease in extracellular fluid volume? action?
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renin
catalyzes rate limiting step in syn of Angio II |
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action of Ang II?
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activates zona glomerulosa of adrenal cortex by binding to GqPCR's
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once AngII Gq alpha subunit activates PLC what happens?
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PIP2 is hydrolized to IP3 and DAG
IP3 incrases intracellular Ca influx by inducing Ca release from ER Ca binds to Calmodulin inducing syn of StAR which lets cholesterol into mt!! |
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besides AngII, what is also a impt regulator of aldosterone syn?
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K: activates v-gated Ca channels in zona glomerulosa
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what is the specific aldosterone binding protein in the blood?
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there is NOT one! 40% of aldosterone is free 50% bound to albumin
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what enzyme is involved in the syn of both aldosterone and cortisol?
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21 hydroxylase
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2 major actions of aldosterone?
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to conserve body Na
maintain extracellular fluid vol |
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what is the principal site of aldosterone action?
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kidney
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waht is the principal action of aldosterone?
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to induce Na reabsorption by the kidney by inducing expression of Na channels to be inserted in apical membane of principal cells of collecting duct and Na/K channels in the basolateral surface
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how are Na channels synthesiszed in response to aldosterone?
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in principal cells of CD of kidney, aldosterone binds MR which binds response element on DNA to cause transcription of protein levels that increase syn of Na channels and increase activity of Na/K ATPase
**aldosterone works at the gene level |
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mineralcorticoid R can be bound by what 2 hormones?
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aldosterone and cortisol with equal affinity but there is 100x more cortisol
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what is HSDII?
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enzyme that converts cortisol to cortisone
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what happens in response to aldosterone excess?
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initially there is increase Na reabosrption, fluid retention
after a few days Na retention ceases bc increased BP causing a compensatory incresae in Na and water excretion by kidneys in spite of elevated aldosterone=aldosterone escape** |
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what happens to Na excretion b/c of aldosterone escape? K?
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Na starts being excreted b/c of compensation due to increased BP
however K ecretion never decreases which can lead to hypokalemia: muscle weakness and mild hyprtension = s/s of hyperaldosteronism |
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what are other targets of aldosterone?
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in addition to its actions on kidney promoting Na reabsorption and K secretin, it does the same actions in salviary glands, sweat glands and colon
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what enzyme is necessary to keep mineralcorticoid target tissues from being overwhelmed by cortisol?
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type 2 11-beta hydroxysteroid dehydrogenase (HSDII) which converts cortisol to cortisone (inactive)
otherwise b/c MR can being both aldosterone and cortisol, the cell would be overstimulated by cortisol since it is 100x more circulating free |
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the principal adrenal androgens are ? secrted as?
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dehydroepiandronsterone (DHEA)
secreted as DHEA sulfate Androstenedione |
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plasma levels of what are a good indicator of adrenal androgen prodxn?
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DHEA sulfate
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how do DHEA and androstenedione activate the androgen R?
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they dont!..they contribute to circulating pool of androgens and estrogens b/c they are converted to these metabolites PERIPHERALLY
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fetal adrenal produces large amts of what? conveted to what where?
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DHEAS
converted to estrogens by the placenta |
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fetal adrenal cortex is composed of what?
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outer neocortex that contains cell that will diff into GFR of cortex..reticularis present at 1yr of age
inner fetal zone which makes DHEAS and involutes at birth |
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what is adrenarche? when does it occur?
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up until 7-8 yrs age, ciculating levels of androgens are steady then they rise continullay thru adolescence then decline starting in 3rd decade of life
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is adrenarche involved with initiation of puberty?
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NO!
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describe the importance of adrenal adrogens in males vs females
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males: unimpt after puberty b/c so many androgens produced by testes
females: major source of androgenic hormones |
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what is the principal glucocorticoid in humans? wher is it produced?
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cortisol
zone fasciculata and some in reticularis |
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what is the most accurate estimate of daily cortisol output?
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24 hr urinary excretion of unmetabolized cortisol
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if corisol is in 100 greater amt free than aldosterone, why is its potency so low?
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b/c HSDII converts it to cortisone
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ACTH is what?
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polypeptide hormone produced in corticotropic cells of ant pituitary by cleavage of pro-opiomelanocortin (POMC)
*key regulator of cortisol release |
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precursor of ACTH?
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POMC
if cleaved as corticotrope: ACTH released if cleaved as melanotrope: alpha MSH released |
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actions of aCTH are mediated by what?
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cAMP
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acute effects of ACTH? (2)?
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1. hydrolysis of stored CE
2. transport of cholesterol to inner mt mem for conversion to pregnonolone (stimulate StAR syn) |
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chronic effects of ACTH on adrenal (3)?
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hypertrhopy and hyperplasa of cells in zona fasciculata and reticularis
increased syn of steroidogenic enzymes and LDLR incresed BFlow to adrenal |
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what controls ACTH release?
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CRH stimulates ACTH release by corticotrophs
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how does CRH stimulate ACTH release?
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CRH binds ativates adenylate cyclase stimulating cAMP
cAMP activates PKA PKA block K efflux thus depolarizing the membrane which activates L-type Ca channels causing a rise in intracellular Ca levels |
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how does vasopressin affect CRH in response to stress?
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it is synergistic by activating PLC to cleave PIP2 into DAG and IP3 to increase Ca levels
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explain the neg feedback loop of cortisol release
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stress activates CRH release from hypothalamus
CRH stimulates ACTH rlease from ant pituitary ACTH stimulates cortisol release from adrenal cortex cortisol is secreted in pulsatile fashion as cortisol levels rise it inhibits CRH release and ACTH release |
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what is the circadian pattern of cortisol release?
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diurnal: levels highest in the morning and lowest after falling asleep
*8am corisol levels clinically b/c they elevate when you wake up |
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what does hypoglycemia stimulate?
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it is a form of stress thus stimulates release of cortisol
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what does it mean to be permissive?
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it does not initiate a specific cellular process per se, but acts by making sure that the cell has the capacity to fully respond when the process is activated such as by regulating gene exprssion to make sure the target cells express the enyzmes, R's needed
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how is cortisol permissive on the syn of glucagon?
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it induces the activity of glucagon synthase thus having a permissive effect on glucagon and Epi induced glycogenolysis
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what are the 2 biological actions of cortisol?
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both permissive and synergistic (the combined effect of 2 hormones is greater than the sum of their individual effects)
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how does cortisol protect against hypoglycemia?
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1. promotes gluconeogenesisz: promote protein catabolism, induces hepatic gluconeogenic enzymes
2.promotes glycogen syn 3. antagonizes the actions of insulin on glucose metabolism by mobiliziing glucose and stimulating protein breakdown to make glucose *blocks glucose uptake by peripheral tissues and decreases sensitivity of sk muscle and adipose to insulin |
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do circulating levels of cortisol rise during a fast?
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NO! even though cortisol is essential for preventing hypoglycemia
this is b/c when you are fasting you are low on insulin. cortisol normally antagonizes the affects of insulin so during fasting there is nothing to antagonize so levels don't rise |
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how does cortisol effect fat metabolism
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permissive effect on catecholamine-induced lipolysis
when present in excess, cortisol increases body fat content through an effect on appetite and by INDIRECTLY stimulating the release of insulin. |
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how does cortisol increase body fat content?
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through an effect on appetite and by indirectly stimulating release of insulin
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how does cortisol affect proteins and peptides involved in mediating inflammation? what action allows for inflammation to occur?
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stimulates the syn of I-kappaB (inhibitor) that binds to NfkappaB preventing it from binding to its HRE
TNF-alpha and IL-1 work through NfkappaB thus they are inhibited the Ikappa B is p-lated by injury signals that activate IkappaB-kinase. Now NFkappaB can increase transcription of TNFalpha and IL1 |
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besides blocking NFkappaB, how else does cortisol suppres inflammation?
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induce syn of anti-inflam IL-10 and lipocortin
lipocortin inhibits phospholipase A2 thus preventing arachidonic acid to cleave into leukotrienes and prostaglandins |
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what are the 9 overall actions of cortisol?
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1. interacts with other hormones
2. protects against hypoglycemia 3. permissive effect on fat metabolism 4. reqd for response of blood vssls to vasoconstrictors 5. affects CNS: mood and behavior 6. anti-inflammatory 7. immunosupprssive 8. permissive effect on devlopment of lungs and surfactant in fetus 9. puts pt at risk for developing osteoporosis |
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how is cortisol immunosuppressive?
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decrease circulating levels of lymphocytes and eosinophils
induces apoptosis in immature lymphocytes thus decrease size of lymphatic tissues inhibit syn of cytokines |
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excessive use of synthetic glucocorticoids puts pt at risk for what?
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developing osteoporosis b/c corisol inhibits Ca uptake by intestine, Ca reabsorption by kidney, bone forming activity of osteoblasts
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primary adrenocortical insufficiency AKA?
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Addisons disease-defect w/n adrenal gland by Tb, tumor, autoimmune disorder**
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what are the 5 cardinal signs of Adrenal insufficiency?
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1. weakness-cortisol def
2. hyperpigmentation-excessive ACTH 3. hypotension-lack of aldosterone 4. nausea and vomiting 5. vitiligo |
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ACTH ___ pigmentation?
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increases b/c POMC cleaved to ACTH which induces expression of pigment thus hyperpigmented in Addison's disease
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what are the aldosterone consequences of adrenal insufficiency ?
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decreased renal reaborption of Na = hyponatremia, depletion of total body Na, polyuria
extracellular fluid depletion-hypotension, dehydration |
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what are the cortisol consequences of adrenal insufficiency ?
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inability to handle stress
hypoglycemia when strssed weakness hypotension decreased appetite hyperpigmentation caused by excessive ACTH secretion GI discomfort |
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what is secondary adrenocortical insufficiency caused by? compared w/ primary?
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insufficient prodxn of ACTH by pituitary LOW ACTH
*pituitary H is the problem primary: adrenal gland itself is destroyed thus HIGH ACTH |
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what is the result of long Tx with synthetic glucosteroids?
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ACTH will decrease b/c corisol levels rise
adrenal could atrophy thus keep stress low b/c could become hypoglycemic |
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what is happening in Cushings syndrome?
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excessive coritsol secretion
major causes #1: ingestion of pharmacological doses of glucocorticoids (low ACTH) 2. excessive secretion of ACTH by pituitary (high ACTH)-Cushings 3. ectopic, ACTH secreting tumor (high ACTH) 4. tumors of adrenal cortex (low ACTH) |
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what are some impot clinical features of Cushing's?
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obesity-trunk
hypertension: increase sensitivity of vssls to catecholamines glucose intolerance: cortisol blocks uptake glucose hirsutism:growing hair where normall doesn't grow due to androgens purple striae: breaks down skin, protein *catabolic osteoporosis: block Ca uptake poor wound healing: cortisol inhibits mediators of inflammation weakness: loss of muscle mass |
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Primary hyperaldosteronism is AKA?
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conn's syndrome
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most common cause of primary hyperaldosteronism? symptoms?
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Conn's syndrome: adenoma of zona glomerulosa
hypertension hypokalemia |
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cause of secondary hyperaldosteronism?
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inappropirate activation of renin-aldosterone system (renin secreting tumor)
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congenital adrenal hyperplasia deficiecies are transmitted?
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AR
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what happens with a CAH with mutation in 21hydroxylase?
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decrease cortisol and aldosterone
increase sex hormones b/c pathway shunted *androgen excess females: fusion of labia and clitoral hypertrophy. breast development and mensturation do not occur males: premature closure of epiphyseal plate, early maturation of genitalia |
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what is a common feature of CAH?
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defect in syn of cortisol leading to rise inACTH and hyperplasia of adrenal
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why is a boy with CAH taller than his brother?
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incrase sex steroids stimulates the release of GH
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what is the only source of circulating epinephrine
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adrenal medulla
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what cells secrtete catecholamines?
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chromaffin cells of adrenal medulla that are postganglionic cells w/ no axons
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what is the rate limiting step in cat synthesis?
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the first step: conversion of tyrosine to DOPA by tyrosine hydroxlase
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waht is dopamine converted to and where? how does it enter?
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dopamine converted to NE in chromafin granule
dopamine enters granule by VMAT (vesicular monoamine transporter) that is a cat-H exchanger |
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to become epi, what must NE do?
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leave chromafin granule to enter cytoplasm where PMNT converts it to Epi
epi then enters granule via VMAT where it is stored |
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where are cats stored?
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in chromaffin granulesin a complex with ATP, Ca and water soluble proteins called chromogranins**
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where does most of Epi and NE come froem?
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Epi:all from adrenal medulla
NE: 70% from nerve terminals |
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how is the syn of cats inhibited?
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feedback inhibited :cats inhibit tyrosine hydroxylase
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how is the adrenal medulla activated?
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with the rest of the sym nervous system
but may be activated on its own the rate limiting step: tyrosine hydroxylase is activated by sns stimulation via Ach |
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effect of cortisol on cats?
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induces PMNT to convert NE to Epi
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how are cats released?
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by exocytosis
b/c chromaffin cells are postganglionic, Ach from pregang binds to R's and promtes Na influx depol membrane and activating Ca which triggers exocytosis |
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which of the cats protect against hypoglycemia?
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Epi
it is sharply increased after insulin injxn b/c cortisol stimulates PMNT to convert NE to Epi *if diabetic, the actions of cats are more impt than glucagon |
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what 4 hormones fight hypoglycemia?
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1. GH
2. glucagon 3. Epi 4. cortisol |
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principal enyzmes of cat degradation?
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MAO monoamine oxidase **in neuronal tissues
COMT cat O methyltransferase *in non-neuronal tissues |
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what is the prinicpal degradative cat enzyme in Neuronal tissue? non-neuronal?
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neuronal: MAO
non: COMT |
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what are the end products of cat breakdown?
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vanillylmandelic acid
metanephrines both conjugated and excreted in urine |
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the actions of cats are mediated by?
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adrenergic R's
alpha 1/2 beta 1/2 |
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mxn of action of alpha 1 adrendergic R?
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increase IP2 and DAG
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mxn of action of alpha 2 adrenergic R?
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decrease cAMP
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mxn of action of beta 1/2 adrendergic r's
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increase cAMP
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what is a pheochromocytoma?
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cat producing tumor of chromaffin cells of the adrnal medulla
most freq released: NE |
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what secretory product of thyroid follicles represents 90% of thyroid output?
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thyroxine (T4) while T3 represents only 10% of thyroid output
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80% of T3 is derived from where?
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T4
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what is rT3?
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less than 1% output
biologically inactive |
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an enlarged thyroid gland is called a ?
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goiter: goiter does NOT describe the fxnl state of the thyoid
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where is TG?
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colloid of thyroid follicle
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where is the iodide pump involved in iodide trapping/
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basolateral surface and is driven by the Na gradient of the Na/K atpase
iodide pump: 2 Na in/ i I in |
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where is TG released upon exocytosis? into where?
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exocytosed from apical surface of cell into colloid..it must be iodinated as it enters colloid ..the Iodide pump is located on basolateral surface
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what can inhibit the iodide pump?
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percholate (HCLO4) **competes with I for pendrin channel
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how can one asscess the capacity of the thyroid to take up iodide?
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inject iodide into pt, scan transporter activity
nl: 20% of circulating pool should be extracted hypothyroid: extract less I the problem with using radioactively labeled I is that it can destroy thyoid cells therefore use TClO4 b/c won't be incorporated into thyroid like I |
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what is the pendrin?
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iodide channel located on apical surface that allows pumped in I to exit thryoid cells into follicular lumen
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how much of the circulating pool of I is normally extracted?
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20%
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the iodination of tyrosyl residues of TG is called what? when does it occur?
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organification
occurs as TG is extruded into follicular lumen |
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one monoiodinotyrosine peptide combines w/ diiodotyrosine to form what?
|
T3 triiodotryosine
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what is the enzyme that iodinates TG to form MIT and DIT?
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thyroid peroxidase
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what are the 3 inhibitors of I uptake?
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HClO4 (percholate)
TcO4 (pertechnetate) CNS- (thiocyanate) |
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as iodide exits through pendrin, what happens?
|
it is oxidized to a cmpd w/ a higher oxidation state as it is exposed to H2O2
H2O2 acts like electron acceptor |
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what enzyme couples MIT and DIT to form T3 and T4?
|
thyroid peroxidase
T4 is formed by DIT + DIT T3 and rT3 : MIT + DIT |
|
|
why is iodination not done w/n thyoid cells?
|
If I was inside the cell it could iodinate impt proteins
|
|
|
where is thyroid H stored?
|
outside the cell in colloid
|
|
|
what is the primary thyroid secretory product?
|
T4 (prohormone) T4-T3
|
|
|
what happens after iodination of TG?
|
endocysosis of follicle containing iodinated TG into apical surface by pseudopod extension
this intracellular colloid droplet is then guided by cytoskeletal components and fuses with lysososme. T3 and T4 are then released |
|
|
how do T3 and T4 exit basolateral surfacee of thyroid cells?
|
by diffusion into fenestrated capillaries
|
|
|
what happens to the extra MIT and DIT after the T4 and T3 are released?
|
MIT and DIT are deiodinated to conserve iodide
*this is the major source of iodide for thyroid hormone syn |
|
|
what is the major source of iodide for thyroid hormone syn?
|
deiodinated MIT and DIT
|
|
|
ppl who are deficient in deiodinases have what symtoms?
|
they cant deiodinate MIT or DIT which is the major source of iodide therefore they have iodide def and excrete MIT and DIT in urine
|
|
|
T3 and T4 are transported mostly how?
|
bound to plasma proteins:
Throxine Binding Globulin (TBG) Transthyretin Albumin free |
|
|
75% of thryoid H is bound to?
|
thyroxine binding globulin
|
|
|
circulating levels are greater for T4 or T3? why
|
T4
binds more tighly to binding proteins thus has longer circulatory half life |
|
|
the biologically available fraction of circulating thyroid hormone is equal to what?
|
the free fraction plus albumin bound fraction
|
|
|
circulatory half life of T4 vs T3?
|
T4: 6-7 days
T3: 1 day |
|
|
all plasma T4 comes from where?
|
thyroid gland
|
|
|
what percent of T3 comes from thyroid? from tissue T4?
|
thyroid: 20%
tissue T4: 80% |
|
|
the majority of rT3 comes from where?
|
95% from tissue T4
**most T3 and rT3 are formed by the peripheral metabolism of T4 |
|
|
what are the major sites of T4 conversion to T3 and rT3?
|
liver
kidney |
|
|
what is the major fxn of Type I deiodinase?
|
to provide circulating T3
|
|
|
major fxn of Type II deiodinase?
|
keep intracellular levels of T3 constant in specific tissues such as CNS
converts T4-T3 |
|
|
most T4 is metabolized by ____ degradation into what?
|
stepwise
thryonine which is excreted in urine or bile |
|
|
why can T4 be taken orally?
|
it is resistant to intestinal and hepatic degradation
|
|
|
what percent of I obtained from stepwise deiodination is recycled back to thyroid?
|
20% b/c this is the normal amt that pendrin removes
|
|
|
when does type II deiodinase increase?
|
when circulating T4 levels fall?
|
|
|
where are type II and type III deiodinases found
|
type II: pituitary
type III: placenta |
|
|
sole fxn of type III deiodinases?
|
hormone inactivation
|
|
|
the most impt regulator of thyroid fxn is?
|
TSH (thryrotropin) secreted by ant pituitary
|
|
|
what are some things that TSH promots?
|
iodide trapping
TG and TPO syn endocytosis of colloid |
|
|
how does TSH act on thyroid cells?
|
Gprotein mediated increase in adenylyl cyclase activity
|
|
|
what (2) governs the secretion of TSH by ant pituitary?
|
TRH
negative feedback inhibition by thyroid H at pituitary and hypothal |
|
|
what is the mxn of TRH action?
|
TRH binds to TRHR activating G protein. this activates PLC and hydrolysis of PIP2 into IP3 and DAG. this leads to a rise in cytosolic Ca and activation of PKC
this stimulates TSH syn and release |
|
|
T3 and T4 exert neg feeback effect on what?
|
TSH releas
|
|
|
what is the principel event in the neg feedback effect on TSH release
|
conversion of T4-T3 and binding of T3 to thyroid HR
genes for alpha and beta subunits of TSH have T3 response elements in their promotor regions which are inhibitory T3 also downregulates TSH R |
|
|
although neg feedback of Thryoid H release occurs at pituitary and hypothalamus, the principal regulatory effect is at what level?
|
level of the pituitary
|
|
|
what is the wolf-Chaikoff effect?
|
when there is too much I inside follicle cell, there is an ACUTE effect that suppresses the thyoid H syn
when levels of I decline, the thyroid H syn resumes |
|
|
clinically, how would you induce a short term inhibition of thyroid hormone prodxn?
|
induce Wolf-Chaidkoff effect by giving excessive levels of I
induce thyroidtoxic condn |
|
|
why is T3 more biologically active?
|
b/c T3 is less tightly bound to circulating binding proteins than T4 and much of the T4 is converted to T3
T3 binds with more affinity to THR |
|
|
which thyroid H is referred to as a prohormone?
|
T4 b/c most T4 activity can be accounted for on the basis of its conversion to T3
|
|
|
where are thyroid hormone R located? what do they act as?
|
in the nucleus where they act as TF
|
|
|
unlike steroid HR, what is uniquie about thyroid HR?
|
associated with HRE even in unactivated state/unbound
|
|
|
what is impt about the THR?
|
**regulates gene transcription
|
|
|
describe the binding of thyroid HR to thyroid response element.
|
binds as HETEROdimer w/ retinoid X receptor (RXR)
|
|
|
effect of unoccupied thyroid HR ?
|
supppressive affect on transcription, but when T3 binds, co-repressors dissociate and co-activators bind
|
|
|
how does T3 neg feedback inhibit TSH release?
|
there are genes for alpha and beta subunits of TSH that have T3 response elements that are inhibitory
|
|
|
in the absence of T3 , what is bound to the Thyroid HR?
|
corepressors that assemble into complex that includes HDAC. this causes deacetlyation that promotes a tighter interaction b/n histones and DNA thereby repressing gene trascription
|
|
|
in the presence of T3, what is bound besides T3 to thyroid HR?
|
coactivators: HAT which lessens the interaction b/n DNA and histones and permits access of TF to regulatory sites
|
|
|
thyroid H affect what tissues?
|
almsot every tissue in body
|
|
|
what specific genes does thyroid H regulate?
|
Na/K ATPase
Beta adrenergic R |
|
|
how does thyroid H affect nervous system development?
|
promotes axon and dendrite growth, synapse formation
MR if absent during fetal life |
|
|
how is thryoid H involved in skeletal development?
|
essential for normal linear growth-
synergistic effect on action of GH affect growth indirectly by enhancing GH syn and release |
|
|
how do thyroid H affect basal metabolic rate?
|
increase
increase HR and force of contrxn increase mobilization of nutrients enhance glucose uptake by gut increase # of mt therefore increasing O2 consumption |
|
|
what is BMR?
|
energy required to maintain bodily fxns at a state of complete rest
thyroid H incresaes BMR indirectly meaured using O2 consumption |
|
|
compare O2 consumption in hypothyroid? hyper?
|
hypo: decresae O2 consumption
hyper: increase O2 (therefore increase BMR) due to incresae in activity of Na/K ATPase by thyroid H |
|
|
what happens if food intake is not increased when thyroid h are elevated?
|
protein and fat stores will be catabolized and weight will be lost
this is b/c thyroid H potentiates the action of hormones on gluconeogenesis, proteolysis and lipolysis |
|
|
how are thyroid H and catecholamines similar?
|
both have similar stimulatory effects on rate of metabolism, heat prodxn, heart rate, CNS activity
thyroid H potentiate the effects of cats on lipolysis, glycogenolysis, and gluconeogenesisw |
|
|
when does congenital hypothyroidism occur? (4)
|
1. aplasia of thyroid tissue
2. enzyme defect in biosyn pathway of thryoid H syn 3. maternal antibodies from mom with autoimmune thryoid disease 4. iodide def |
|
|
what are the 3 types of aquired hypothyroidism?
|
primary *autoimmune-thryoid directly affected
secondary: pituitary is affected tertiary: something wrong in hypo |
|
|
waht is the cause of primary hypothyroidism?
|
thyroid is directly affected
1. (primary cause) autoimmune condition that leads to destrxn of thyroid gland *most common cause of hypothyroidism in US anti-thyroid Ab 2. iodide def w/endemic goiter due to low iodide, decreased T4 thus increased TSH ouput(3rd world) 3. iatrogenic: surgical removal of thyroid |
|
|
waht is the cause of secondary hypothyroidism?
|
pituitary is disfxning
dimished TSH released |
|
|
what are some s/s of hypothyroidism?
|
impaired memory, confusion
muscle weakness slowed heart rate anemia low BMR intolerance to cold *myxedema: non pitting |
|
|
what is myxedema?
|
*assoicted with hypothryoidism
non pitting edema caused by accumulation of mucopolysaccharides in CT spaces thickend skin, enlarged tongue, puffy eyes |
|
|
what is throtoxicosis?
|
decrease TSH incrase T4
when tissues are exposed to excessive amts of thryoid H causes: Grave's, Plummers, Toxic multinodular goiter |
|
|
what is the most common cause of thyrotoxicosis?
|
Grave's Disease (autoimmune)
hyperplastic goiter TSH levels are suppressed b/c high levels of thyoid H *throid-stimulating Ig (TSI) that binds to TSHR stimulating R for 10-12 hrs (TSH effects only last 1hr) |
|
|
what is thyroid stimulating Ig?
|
Ig found in ppl with Grave's disease
binds TSH R and induces TSH-like effects but stays attached for 10-12 hrs |
|
|
what are the 3 causes of thyrotoxicosis?
|
graves
plummers toxic multinodular goiter |
|
|
in addition ot having symptoms associated with thryotoxicosis, pts with Grave's exhibit what?
|
exophthalmos: protrusion of eyeballs due to edematous swelling and deposition of large quantities of mucopolysacchs in retroorbital tissues
*due to autoAb |
|
|
is there a genetic component to Grave's?
|
yes
members of families may have other organ-specific autoimmune disorders |
|
|
what does the Y chromosome contain?
|
regions that are homologous to X (PAR region)
Y chromosome spcefic: SRY |
|
|
what is the SRY gene and what is its fxn?
|
located next to PAR of the short arm
product: DNA binding protein that promotes the differentiation of testes |
|
|
describe the X chromosome in somatic cells
|
only one X is active
|
|
|
when does X inactivation occur?
|
late blastocyst stage
random |
|
|
is the PAR inactivated during X chromosome inactivation?
|
no
|
|
|
whre does meitotic crossing over occur and when?
|
b/n X and Y in PAR during spermatogenesis
|
|
|
if the SRY is lost during crossing over and ends up on X chromosome, what happens?
|
person becomes male
|
|
|
47XXY is what?
|
Klinefelter's
testes develop but dysgenesis of seminiferous tubules b/c no AMH |
|
|
45XO is what?
|
Turner's: germ cells absent therefore developing ovary will regress
|
|
|
when can mosaics occur?
|
if nondisjxns occur in early mitotic division
|
|
|
what is the anlagen?
|
embryonic structures that are identical in genetic males and females
|
|
|
what determines the differentiation of GONADAL anlage?
|
the chromosomal content of the tissue
|
|
|
what determines the differentiation of Reproductive tract and external genitalia?
|
the fetal hormone prodxn
|
|
|
what does the gonad look like in early embryonic development?
|
outer cortex (develops into overy)
inner medulla (develops into testes) |
|
|
when will the indifferent gonad develop into a testis?
|
expression of SRY gene: determined by the chromosomal content of the tissue
|
|
|
when do primordial germ cells migrate to the indiffernt gonad and what is this required for?
|
5-6 week old embryo
invasion of the germ cells into the undifferntiated gonad is required for the formation of an ovary but NOT a testes |
|
|
if primordial germ cells don't make it to genital ridge what happens?
|
ovary wont' develop b/c invasion is required to develop into ovary
|
|
|
what total is reqd for ovarian differntiation?
|
2Xchromosomes in the absence of the SRY gene
**the inactivated X is activated again in the primordial germ cells when they enter the genital ridge |
|
|
what happens to inactivated X chromosomes as they enter the genital ridge?
|
they are reactivated thus now you have 2X chromosomes reqd for ovarian differentiation
|
|
|
when are leydig cells secreting testosteron as opposed to when oogenesis begins?
|
testosteron: 8-9weeks
oogenesis: 11-12 weeks |
|
|
what is the first indicator of ovarian differntiation?
|
onset of meiosis
|
|
|
what do Mullerian and Wolfian ducts develop into?
|
Mullerian: fallopian tubes, uterus, cervix
Wollfian: epididymis, vas deferens, seminal vesicles |
|
|
development of the male genital tract depends on what?
|
secretion of
AMH testosterone |
|
|
if AMH is secreted what happens?
|
mullerian ducts are regressing at 8 weeks
|
|
|
what cells produce AMH?
|
sertoli cells of the fetal testis
|
|
|
if AMH is secreted the Mullerian ducts regress at 8 weeks, but when do the Wolfian begin to differentiate?
|
at 9 weeks in response to testosterone **need to be stimulated by testosteron
|
|
|
in the absence of testosterone what happens to ducts?
|
Wolfian ducts will regress
|
|
|
when do the genital anlagen develop into male structures and what stimulates them to do so?
|
8-12 weeks
androgen stimulation is REQD |
|
|
what androgen is necessary for the development of anlagen into male structures? how is it obtained?
|
DHT (testosterone is necessary for Wolfian ducts)
Testosterone is converted to DHT by 5alpha reductase |
|
|
waht enzyme converts testosterone to DHT? what happens in its absence
|
5 alpha reductase
w/o 5alpha reductase, genetic males will have male internal reproductive tract, but female external genitalia |
|
|
in the absence of DHT, what happens to GENITAL anlagen?
|
develop into female genitalia
|
|
|
what is cyrptorchidism?
|
failure of at least on testis to not descend into scrotum
|
|
|
what is the disorder of gonadal differntiation associated with seminiferous tubule dysgenesis?
|
Kleinfelters
|
|
|
what is the disorder of gonadal differntiation associated with gonadal dysgenesis?
|
Turner's: XO
|
|
|
how does a 46XY individual look?
|
normal testes
female external genitalia internal genital tract poorly developed (due to enyzmatic defect, androgen R defect, 5alphareductase deficiency) |
|
|
what is the problem with 46XX?
|
female pseudohermaphrodite
exposure of fetus to excessive androgen stimulation in utero |
|
|
the fxn unit of the ovary is what? waht are the structural features?
|
follicle
thecal cells form the outer surface-steroid H syn granulosa cells: make steroid H oocyte-female gamet fluid filled antrum |
|
|
what are the 3 principal steroid hormones secreted by the adult ovary?
|
1. estradiol
2. progesterone 3. androstenedione |
|
|
what is the principal ovarian estrogen? what is the most potent?
|
both are estradiol (E2)
|
|
|
what is the principal estrogen in post menopausal women?
|
Estrone (E1)
|
|
|
what estrogen is produced in large amts by placenta during pregnancy?
|
Estriol (E3)
|
|
|
estrogen biosyn involves what cells?
|
interstitial cells of theca interna and ovarian stroma
granulasa cells |
|
|
what do the Interstitial cells of the theca interna and ovarian stroma synthesize?
|
ANDROGENS **primarily androstenedione
precursors for estrogen syn low levels of testosterone formed b/c thecal cells are deficient in 17b-hydroxysteroid dehydrogenaes activity |
|
|
why are only low levels of testosterone formed in thecal cells?
|
they do NOT have 17b-hydroxysteroid dehydrogenaes activity which means they can't convert androstenedione to testosterone
|
|
|
what can thecal cells NOT make?
|
testosterone
cannot convert androgens to estrogens (they make androstenedione) |
|
|
why can't theca interna cells not convert androgens to estrogens?
|
b/c they lack aromatase
aromatase is necesary to convert testosterone to estradiol |
|
|
action of aromatase?
|
convert testosterone to estradiol
|
|
|
compare the vasculature of theca layer to granulosa layer?
|
theca: highly vascular
granulosa: no vascular |
|
|
can granulosa cells convert 21-carbon precursors (pregnonlone and progesterone) to androgens?
|
NO! this happens in thecal cells
|
|
|
what is the action of granulosa cells?
|
high aromatase therefore can convert androgens from thecal cells into estrogens
17b-hydroxysteroid dehydrogenaes activity therefore can convert androstenedion to testosterone |
|
|
do thecal cells or granulosa cells have more LDL receptors?
|
thecal thus they can produce more progesterone to make androstenedione
|
|
|
what is the major estrogen produced in granulosa cells?
|
estradiol
*androstenedione is teh major androgen produced by the thecal cells |
|
|
what is the hormone that stimulates the uptake of LDL?
|
LH in interstital cells of theca interna
lesser extent: FSH in granulosa |
|
|
actions of FSH and LH are mediated by?
|
cAMP
|
|
|
net effect of LH stimulation of insterstital cells is? net effect of FSH stimulation iof granulosa cells is what?
|
LH: androgen syn
FSH: estrogen |
|
|
what are progestins? waht are the major ovairan progestins?
|
steroids that promote gestation
progesterone and 17alpha-hdyroxyprogesterone *progesterone is most potent |
|
|
what is the principal source of progesterone in non pregnant adult?
|
corpus luteum
|
|
|
waht is the principal circulating androgen in women?
|
testosterone
|
|
|
estrogen stimulates the syn of what R?
|
progesterone R in progesterone responsive tissues
|
|
|
compare gonadotropin levels during gestation, childhood, puberty, reproductiv years, menopause
|
gestation: FSH > LH
childhood: low levels; FSH>LH puberty: nocturnal release LH reproductive: LH > FSH menopause: FSH > LH (like gestastion) |
|
|
when are gonadotropin levels low?
|
during childhood
the hypothalamic-pituitary axis is more sensitive to feedback inhibition by sex steroids than in aduls |
|
|
what is an early indicator of puberty?
|
a sleep associated surge of LH
hypothalamic-pituitary axis less sensitive to feedback inhibition |
|
|
when do you have an orderly cyclic release of gonadotropins?
|
reproductive years LH > FSH
LH released both day and night |
|
|
when does follicular phase begin? describe the lenght
what phase of the endometrial cycle does it correspond with? |
onset of menstural bleeding
variable in length correspnds w/ proliferative phase of endometrial cycle |
|
|
lenght of luteal phase? when does it end? what phase of endometrial cycle does it correspnd with?
|
constant lenght (13-14 days)
ends w/ onset of next menses correspnds w/ secretory phase of endometiral cycle |
|
|
what is the primordial follicle?
|
basic fxnl unit of ovary
respresents NONgrowing follicles in the outer cortex of ovary |
|
|
after primordial follicles are formed, at what stage of meisosi are they arrested in?
|
Prophase I of meiosis by oocyte maturation inhibitor
|
|
|
waht is thought to initiate the growth of primordial follicles?
|
intraovarian signals that are the driving force for primordial follicles to continue to grow into early antral follicle W/O gonadotropin stimulation!!
|
|
|
zona pellucida surrounds ?
|
primary follicle
|
|
|
how long does it take for the primordial follicle to become primary follicle?
|
long..months
|
|
|
waht is the size of the preantral follicle as it begins to grow? waht does it consist of?
|
0.2mm
granulosa layer (avascular)cells express FSH, estrogens and androgen R's growing thecal layer w/ vascular supply* that express LH R |
|
|
does the follicular growth from primordial follicle to preantral follicle require gonadotropins?
|
no..gonadotropin independent
|
|
|
waht develops in preantral follicle after 25 days?
|
antrum now called antral follicle due to expresssion of aquaporins by granulosa cells
|
|
|
waht is the progression of follicles from primordial?
|
primoridal - preantral-antral-proovulatory
|
|
|
how long does it take for 0.2mm follicle to reach preovulatory status? describe gonadotropin stimulus during this time
|
85 days
first 65 days: no gonadotropins last 20 days: gonadotropin-dependnet **majority of growth during the first 65 days is FSH-independent |
|
|
what happens to growing follicle in absence of FSH?
|
undergo atresia
|
|
|
what is it called when a follicle is recruited for ovulation? when does this occur?
|
cyclic recruitment
late luteal phase of preceding cycle |
|
|
when is the dominant follicle selected?
|
early follicular phase of current cycle
|
|
|
when does ovulation occur?
|
10-14 days after dominant follicle is selected
during this time the follicle grows which is dependnt on presence of gonadotropins |
|
|
how does the dominant follicle inhibit the development of less mature follicles?
|
suppressing FSH secreteion as a result of prodxn of estrogen HOW?
1. granulosa cells become more sensitive to FSH by upreg FSH R's 2. FSH stimulates expression of GF such as IGF-2, inhibin, activin to sustain growth 3. FSH induces the formation of LH R's in granulosa cells so follicle can be supported by both gonotrophs! |
|
|
what is atresia? waht opposes this?
|
apoptosis of follicles
affects oocyts and granulosa cells FSH is anti-apoptotic by inducign antiapoptotic genes promote atresia: TNFalpha, androgens |
|
|
what happens to the follicle as it prepares to ovulate?
|
increase in antral fluid
gap jxns linking granulosa cells are lost edema in theca interna stigma forms granulosa cells spread apart |
|
|
what is the signal requd to induce ovulation? what causes this?
|
LH surge that is the result of a POSITIVE feedback effect of estradiol on the pituitary/hypothal
*peak estrogen prodxn precedes LH peak |
|
|
waht does LH stimulate in preovulatory follicle?
|
resumption of meiosis, ovulatin and leutinization of follicle
|
|
|
what 2 proteins are reqd for ovulation and what induces them?
|
LH induces:
1, progesterone R: induces proteases that digest proteins in wall of follicle (matrix MMPs called ADAMTS-1 and cathepsin-L) 2. COX-2: formation of PGE2 (prostaglandin) |
|
|
waht causes expansion of cumulus oophoris in preovulatory follicle?
|
LH by inducign progesterone which induces expression of matrxi MMPS: ADAMTS-1 and cathepsin-L that break down follicle wall
|
|
|
waht suppresses the release of oocyte maturation inhibting substance (OMI)?
|
LH in order to reinitiate meiosis and form secondary oocyte and first polar body
|
|
|
after ovulation and completion of first meisois division. what occurs?
|
formation of secondary oocyte
MII proceeds to Metaphase II where secondary oocyte is arrested until fertilization |
|
|
primary role of oxytocin? addittional role?
|
eject milk from the lactating mammary gland
stimulate contrxn of uterus |
|
|
action of somastatin vs somatotropin (GH)
|
SS: inhibit growth by inhibiting GHRH stimulation
GH: stimulates growth and development |
|
|
what cells produce GH?
|
somatotrophs: most numberous cells in pituitary
|
|
|
what is the affect of short term fasting and prolonged protein calorie deprivation on GH secreteion
|
increase GH secretion
|
|
|
insulin growth factors (IGFs) are produced by many tissues in response to what?
|
GH
IGF-1 is greatly reduced in the plasma of GH-deficient subjects |
|
|
what are the fxn of IGF's?
|
mediate the typical GH proliferative effects on cartilage, bone, muscle, adipose tissue
ppl who lack ability to produce IGF's have retarded growth despite high GH levels they also stimulate the precesses of anabolism |
|
|
what causes teh release of ADH or oxytocin into post pituitary?
|
AP from hypothalamus causes discharge
|
|
|
which motivated behavior is very tightly regulated?
|
thirst
|
|
|
afferent signals to hypothalamus are modulated by local concentrations of ?
|
NE, Serotonin, ACh, dopamine
|
|
|
in ant pituitary, one cell type produces how many hormones?
|
only 1
|
|
|
gonadotrophs in ant pituitary producde what?
|
FSH, LH
|
|
|
thyrotrophs in ant pituitary produce waht?
|
TSH
|
|
|
Lactotrophs in ant pituitary produce waht?
|
Prl
|
|
|
Corticotrophs in ant pituitary release what?
|
ACTH
|
|
|
insulin growth factor (IGF-2) is present mostly in?
|
infant
|
|
|
GH acts on liver to produce waht?
|
IGF's
|
|
|
what time of day is cortisol released?
|
during eary morning hours (8am) after ACTH release
|
|
|
waht type of metabolism does GH "prefer"
|
more fat metabolism and less carbo metabolism
|
|
|
waht does GH oppose?
|
insulin
induces resistance to action of insulin by inhibiting glucose uptake by muscle and adipose cells, enhances lipolysis. Acts to increase plasma levels of FFA and descrese adipose tissue. |
|
|
actions of GH ? (5)
|
healthy ANABOLIC actions
1. anti-insulin: incresae plasma glucose 2. incresae linear growth 3. increase lean body mass 4. decrease adiposity 5. increase organ size, increase organ fxn |
|
|
describe the GH secretion
|
pulsatile, mainly during sleep
|
|
|
why is it easier to measure IGF-1 than GH?
|
b/c IGF-1 is in nm (10^-9) not pmol (10^-12)
|
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|
what is requd for gene expression of GH besides GH?
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pituirtary transcription factor (Pit-1)
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what are the 2 hormones that regulate GH?
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GHRH +
SS - |
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what must happen when GH binds to target cells?
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cross linking of 2 receptors
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what actions of GH are mediated by IGF's?
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all growth stimulating hormones (not metabolic actions)
IGF itself may act in endocrine, paracrine, and autocrine manner |
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in the tissuees, GH action is mediated by _____ IGF-1
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locally produced IGF-1 and therefore GH activity may not at all be related to the circulating level of IGF or GH
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waht does IGF compete for ?
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insulin R
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explain the differences b/n insulin and IGF's
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insulin: made in pancreas
expressed in picomolar amts T1/2 minutes IGF: mane in liver, but also locally expressed in nanomolar T1/2 is hours b/c boutnd to IGF-binding proteins |
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when is IGF biologically active? what do they bind to?
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only the FREE IGF
bind to tyrosine-kinase R's with cross reactivity in binding |
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which agents other than GH stimulate IGF prodxn in bone?
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PTH
sex steroids |
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in reproductive system, IGF is produced from?
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produced locally from sex steroids
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what happens to GH during stress?
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GH is reduced
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what factors decresae GH?
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undernutrition/fasting/ starving which cause decrease IGF, IGF R's which leads to catabolic actions
Trauma: GH decrease, IGF decresae |
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pre puberty excess GH is called wht? post puberty?
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pre: gigantism
post: acromegaly |
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what are the metabolic affects of excess GH?
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constant increase in blood sugar
incresaed insulin leading to Type 2 diabetes more muscle-atherosclerosis |
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excess of what hormone will give you high fasting glucose concentrations, hi insulin secretion but resistance to insulin action?
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excess GH
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cells in the periventricular region release what? neurosecretory cells in arcuate nucleus?
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SS, inhibitor of GH
arcuate: GHRH net affect depends on the ratio |
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IGF inhibits ___ secretion?
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GH
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what is the main stress that INCREASES GH? (all other stress decreases GH)
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acute hypoglycemic stress
this is b/c GH raises glucose |
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what is the affect of exercise on GH?
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exercise stimulates GH increase which stimulates prodxn of IGF therefore good vascular development which leads to less ischemia
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waht is pituitary dwarfism?
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pituitary failure of GH prodxn and consequent proportional redxn in body size
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what is Laron syndrome:
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unresponsivness to live to GH with failure to stimulate IGF-1 prodxn
*have GH, don't make IGF-1 will often have high levels of GH |
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compare levels of GH in GH defienciy v/s GH insensitivity?
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defiency: lo GH leads to low IGF-1
insensitivity: high GH but low IGF-1 b/c defective GH R's therefore get NO negative feedback |
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direct action of GH?
indirect? |
direct: incresae plasma glucose, stimulate lipolysis, decrease peripheral glucose uptake
indirect: by IGF's and are ANABOLIC: IGF increase cartilage syn in epiphyseal plates |
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during puberty, increased androgen secretion increases waht?
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GH secretion
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what steroids are produced in pituitary?
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NONE..only peptides and glycoproteins
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waht are considered pituitary glycoprpotein hormones? what are they composed of?
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FSH
LH TSH composed of 2 subunits: alpha and beta but beta is unique to each hormone |
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action of FSH in males? females?
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males: stimulates sertoli cells to begin spermatogenesis
femles: increse E2 in follicles leading to ovualation |
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action of LH in males? females?
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males: stimulate Leydig cells to secrete testosterone
females: increase E2 for ovulation, progesterone |
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differnt gonadotropins pulse at differnt freq. a faster pulse gives you? slower?
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faster: LH
slower: FSH |
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what affect does excess PRL have on GnRH? how does this affect the gonads?
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decreaes GnRH b/c neg feedback
leads to hypogonadism in both men and women |
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if you have hyperprolactinemia where does teh problem lie?
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with dopamine not being delivered, made,etc
pituitary tumor anti-dopaminergic therapy medications |
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affect of stress on PRL?
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stress causes PRL secretion
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low ACTH causes?
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Addison's syndrome, hyponatremia
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what is the only H of ant pituitary that is secreted in absence of exogenous stimuli (all other H's are secreted in response to releaseing H and regulated by feedback H's)
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prolactin is secreted in the absence of exogenous stimuli
suppressed by dopamine from hypothalamus |
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what is luteinization?
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after ovulation, LH promotes teh differentiation of follicular cells into luteal cells to form corpus luteum
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fxn of corpus luteum?
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produces hormones that favor implantation of an ovum: estrogens and progesterone *mainly progesterone is incresed in luteal phase
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what controls the steroid syn of corpus luteum?
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LH: a drop in LH will cause a rapid decline in hormone prdxn by the corpus luteum
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waht is the life time of the corpus luteum
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constant: lenght of luteal stage = 13-14 days
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what hormone maintains the corpus luteum in nonpregnanct adult?
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hCG
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what inhibin is associated wiht follicular phase? luteal?
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follicular: B produced by granulosa cells
luteal: A formed by corpus luteum |
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waht is a good indicator of granulosa fxn? corpus luteum fxn?
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inhibin B levels during follicular phase
inhibin A to assess LH mediated corpus luteum fxn |
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how does the prodxn of estrogen affect the granulosa cells?
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acts synergistically with FSH to promote granulosa cell proliferation
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why do FSH and estrogen promote LH R' biosyn?
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so that granulosa cells of maturing follicle become sensitive to LH
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when do granulosa cells begin to acquire LH receptors?
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mid follicular phase as they prepare for LH surge
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waht hormone midcycle stimulates GnRH freq?
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estradiol to pos feedbac for LH surge
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prolferative phase of endometrial cycle is analogous to what ovary stage? what is the dominant hormone of poliferative phase?
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follicular which begins with the onset of menses
estrogen is dominant hormone which causes the increase in endometrium |
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secretory endometrial phase is analogous to what ovarian phase? main hormones?
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luteal phase
both estrogen and progesterone from corpus luteum which is regulated by LH |
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release of what caues the endometrium to involute in menstrual phase? (also causes "cramps")
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prostaglandin PGF2a: causes vssls to become spastic and induces uterine contractions
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what is menopause?
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when all fxnl follices are depleted
age 45-55 cessation of menstruation decline in estrogen levels |
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what is the predominant srum estrogen after menopause? where does this come from?
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estrone
derived from peripheral conversion of androgens formed from fat |
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what are the clinical manifestastions of menopause? caused by?
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caused by decline in estrogen
uterine atrophy dryness of vagina gradual loss of bone mass periodic increases in body temp (hot flashes) depression, anxiety, irratibility incresae in circulating levels of gonadotropins (HAVOC) |
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when is the fertilit period?
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2 days before and 1 day after ovultion (ovum only viable 1 day after ovulation)
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at the end of the follicular stage, what is the consistency of the cervial mucus?
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watery to make it possible for sperm to transit the cervical canal
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where does fertilization occur?
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in the ampula of fallopian tube
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steps of fertilization
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1.reach fallopian tube
2. capacitation: ability to fertilize egg-get rid of semen 3. attach to zona pellucida by binding ZP3 to increase intracelluar Ca which fuses PM of sperm with outer acrosomal mem (acrosomal rexn) 4.hydrltyic enzymes in acrosome are released which degrade zona pellucida and sperm cell enters 5.formation of IP3, incresa intra Ca which ends 2nd Meitotic division and causes cortical rxn |
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what happens after sperm enters the cells?
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1. completion of 2nd meitosis of oocyte
2. cortical rxn: hardening of zone pellucida to keep others out |
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fertilization dominated by __ H
implantation dominated by ___ H |
ferti: estrogen
implantation: progesterone |
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what hormone decreases constriction allowing Morula (solid ball of cells) to move down oviduct?
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progesterone
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what is the portion of cells that penetrate the endometrium?
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syncytiotrophoblast: begin to form placenta
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once the blastocyst implants, the stroma forms what?? what are the changes involved?
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DECIDUA
increased edema *vascularization storage of nutrients in stromal cells |
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what maintains the endocrine secretion by the placenta?
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NOTHING
it is autonomous..not regulated by maternal or fetal signals |
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what hormone sustains the corpus luteum for placenta to form?
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hCG
similar to LH in structure secreted by trophoblast cells long T1/2 fxn: prolong life of corpus luteum and stimulate testosterone prodxn by fetus |
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what is the major hormone during pregnancy? produced by?
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estriol produced by placenta
DHEAS from fetal adrenal is then hydroxylated in fetal liver. placenta then removes sulfate and converts it to estriol *2 organs in fetus working to make estriol |
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action of chorionic somatomammotropin (hCS)?
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placental lactogen
acts like prolactin antagonizes teh actions of insulin |
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effct of estrogens on breast development?
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promote growth and branching of duct system in the presence of progesterone
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waht are the 4 hormones that are present for breast develpment during pregnancy?
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estrogen
progesterone prolactin: lobuloalveolar development/promotion of milk secretion human placental lactogen: same as PRL |
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3 hormones that have a permissive effect on brest development?
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GH
cortisol IGF-1 |
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what prevents you from lactating during pregnancy?
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estrogen and progesterone levels
(estrogen sits in prolactin R blocking action) |
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following parturition, what is the most potent stimulus for PRL release?
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suckling
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why after birth do we have a drop in prl?
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you lose placenta which decreases estrogen and progesterone
now nothing is blocking the prolactin R, but PRL is under tonic inhibition by dopamine so the levels are low until sucking stimulates release |
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the principal mxn of PRl action is activation of what pathway?
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JAK/STAT
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