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415 Cards in this Set

  • Front
  • Back
TRH from hypothalamus simulates what?
TSH from ant pituary which then acts on thryoid
Prolactin from ant pituitary which then acts on breasts
TSH has what affect on thyroid?
stimules thryoid to secrete thyroxineT4, triiodothyronine T3
prolactin has what affect on breasts?
stimulate breast development and milk production and in males facilitates reproductive fxn
Dopamine from hypothalamus inhibits what?
inhibits prolactin rlease from ant pituitary
CRH from hypothalamus stimulateas waht?
ACTH release from ant pituiatary to act on adrenal cortex to secrete cortisol
vasopressin acts on what ant pituitary hormone?
ACTH which then tells adrenal cortex to secrete cortisol
what is the affect of SS release from hypothalmus?
inhibits TSH from ant pituitary
inhibits GH from ant pituiatary
what is the affect of GHRH from hypothalmus?
stimulates GH release from ant pituitary
what is the affect of GH?
acts on liver cells to secrete IGF-1
stimulates protien syn
influences carb and lipid metabolism
what is the affect of GnRH from hypothalamus?
stimulates release of LH and FSH form ant pituiatary
what is the blood supply of the ant lobe of pituitary?
ICA gives off superior hypophyseal artery
what is the blood supply of the post lobe of pituitary?
ICA gives off inferior hypophyseal artery
what exists b/n the ant and post lobes of pituitary?
hypophysial-portal vascular connection in the pituitary stalk
vein to vein portal system linking fenestrated capillaries
how do hormones from hypothalamus travel to ant pituitary?
hypothalamic hormones travel to the anterior lobe by way of a special capillary system, called the hypothalamic-hypophyseal portal system.
how do hormones from hypothalamus reach post pituitary?
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.
what are the nuclei associated with the post pituitary?
paraventricular and supraoptic nuclei secrete oxytocin and vasopressin directly into capillaries in the posterior lobe
what are the 6 hormones produed by ant pituitary?
produces six peptide hormones: prolactin, growth hormone (GH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH).
fxn of osteoblasts?
bone forming cells
secrete bone matrix on which Ca and PO4 precipitate
what is an osteoclast? derived from?
large multinucleated cell derived from monocytes
fxn resorb bone
what hormone inhibits bone formation?
what are the 3 regulators of Ca?
Vitamin D3 1,25 dihydroxy
what hormone stimulates Vit D synthesis?
action of 1 aplha hydroxylase?
activates Vit D
PTH stimulates 1 alpha hydroxylase
action of phosphate on 1 alpha hydroxylase?
decresaed levels of PO4 increase 1 alpha hydroxylase
main action of activated Vit D?
stimulate absorption of Ca form liver by stimulating prod of calcium binding protein
what cells produce PTH?
chief cells of parathyroid
when is PTH secrted
inversely related to serum Ca concentration
secreted when Ca is low in plasma
what is the overall action of PTH?
increase plasma Ca levels
decrease plasma phosphate
action of PTH on bone? kidney?
directly affects bone by increasing Ca resorption
reabsorption of Ca in DCT and inhibit reabsorption of PO4
what hormone causes a decrease in plasma Ca?
what cells synthesize and secrete calcitonin
parafollicular cells of thyroid
target cell for calcitonin?
osteoclast causing inactivation
inhibit bone resorption
steroid hormones are derived from the modification of what?
where is most of the cholesterol used for steroid hormone syn obtained from?
circulating LDL
how is cholesterol obtained from LDL?
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
how is cholesterol converted into the CE storage form? how are CE mobilized back into cholesterol?
by acyl CoA: cholesterol acyltransferase
mobilized by cholesterol esterase
where does steroid hormone syn occur?
what enzyme is involved in the first step of steroid hormone syn?
StAR: steroidogenic acute regulatory protein located in inner mt mem.
moves cholesterol from outer mem to inner mt mem
how is StAR activated and newly synthesized?
by cAMP dependent mech that activates PKA
what is the rate limiting step in steroid H syn? where does it occur?
inner mt membrane
cholesterol converted to pregnonolone
what is pregnonolone/
precursor for all adrenal, gonadal, and placental steroids
syn occurs when cell is stimulated
cholesterol esterase is stimulated by?
in terms of steroid H syn, when cAMP increases, PKA is p-lated increasing the syn of what impt protein?
StAR which then promotes the flow of cholesterol into mt
the rate of steroid H syn depends on what
rate of release
there are no special mxns for storing steroid H's (steroidogenic cells DO NOT contain stored hormone)
steroid H are not very soluble in waht solns? how do we solve this problem?
aqueous solns
steroid H are bound to binding proteins
the 3 main specific steroid H binding proteins are?
sex hormone binding globulin (SHBG) binds androgens and estrogens
Corticosteroid binding globulin (CBG)-binds cortisol and progersterone
Vitamin D binding globulin (DBG)
a fraction of steroid H pool binds non-specifically and with low affinity to what?
what is impt about the free fraction of steroid Hormone?
can readily bind to R's in target tissues and induce a physiological response
readily pass through PM
besides the free fraction of steroid H, which other bound steroid H is also readily available to target tissues?
that bound non specifically to albumin b/c of the weak binding
why are steroid H converted to inactive metabolites?
b/c humans do not have enzymes that can degrade the steroid nucleus
what is the prinicipal site of steroid H inactivation?
after steroid H are inactivated in liver, what are they conjugated with?
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
the conjugated inactivated steroid H are excrted prinicipally by what?
what happens to the steroid H that are not inactivated?
they are converted to more active metabolite or metabolit with different action in peripheral tissue (2ndary organ)
what is characteristic of steroid H receptors?
nuclear R's
ligand activated TF
nuclear locatialization signal
when the steroid H binding site is unoccupied, the steroid H R's form large complexes with what?
heat shock proteins
what happens when steroid H binds steroid H R?
the R dissociates from hsp's and forms HOMOdimer with another occupied R for same H
when do steroid H R's bind DNA? when they do bind to DNA, what is the target?
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
what is recruited by steroid H bound dimers that bind HRE?
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
waht is the action of steroid H R antageonist?
incduces conf change in the R that prvents coactivators from binding and favors corepressors
zona glomerulosa secretes?
mineralcorticoids: aldosterone
what is the principal minearlcorticoid in humans?
what is the primary regulator of aldosterone S?
renin-angiotensin system
what makes up adrenal cortex?
zona glomerulosa, fasiculata, reticularis
what is released from the JG cells in response to decreased arterial BP, sympathetics, and decrease in extracellular fluid volume? action?
catalyzes rate limiting step in syn of Angio II
action of Ang II?
activates zona glomerulosa of adrenal cortex by binding to GqPCR's
once AngII Gq alpha subunit activates PLC what happens?
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!!
besides AngII, what is also a impt regulator of aldosterone syn?
K: activates v-gated Ca channels in zona glomerulosa
what is the specific aldosterone binding protein in the blood?
there is NOT one! 40% of aldosterone is free 50% bound to albumin
what enzyme is involved in the syn of both aldosterone and cortisol?
21 hydroxylase
2 major actions of aldosterone?
to conserve body Na
maintain extracellular fluid vol
what is the principal site of aldosterone action?
waht is the principal action of aldosterone?
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
how are Na channels synthesiszed in response to aldosterone?
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
mineralcorticoid R can be bound by what 2 hormones?
aldosterone and cortisol with equal affinity but there is 100x more cortisol
what is HSDII?
enzyme that converts cortisol to cortisone
what happens in response to aldosterone excess?
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**
what happens to Na excretion b/c of aldosterone escape? K?
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
what are other targets of aldosterone?
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
what enzyme is necessary to keep mineralcorticoid target tissues from being overwhelmed by cortisol?
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
the principal adrenal androgens are ? secrted as?
dehydroepiandronsterone (DHEA)
secreted as DHEA sulfate

plasma levels of what are a good indicator of adrenal androgen prodxn?
DHEA sulfate
how do DHEA and androstenedione activate the androgen R?
they dont!..they contribute to circulating pool of androgens and estrogens b/c they are converted to these metabolites PERIPHERALLY
fetal adrenal produces large amts of what? conveted to what where?
converted to estrogens by the placenta
fetal adrenal cortex is composed of what?
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
what is adrenarche? when does it occur?
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
is adrenarche involved with initiation of puberty?
describe the importance of adrenal adrogens in males vs females
males: unimpt after puberty b/c so many androgens produced by testes
females: major source of androgenic hormones
what is the principal glucocorticoid in humans? wher is it produced?
zone fasciculata and some in reticularis
what is the most accurate estimate of daily cortisol output?
24 hr urinary excretion of unmetabolized cortisol
if corisol is in 100 greater amt free than aldosterone, why is its potency so low?
b/c HSDII converts it to cortisone
ACTH is what?
polypeptide hormone produced in corticotropic cells of ant pituitary by cleavage of pro-opiomelanocortin (POMC)
*key regulator of cortisol release
precursor of ACTH?
if cleaved as corticotrope: ACTH released
if cleaved as melanotrope: alpha MSH released
actions of aCTH are mediated by what?
acute effects of ACTH? (2)?
1. hydrolysis of stored CE
2. transport of cholesterol to inner mt mem for conversion to pregnonolone (stimulate StAR syn)
chronic effects of ACTH on adrenal (3)?
hypertrhopy and hyperplasa of cells in zona fasciculata and reticularis
increased syn of steroidogenic enzymes and LDLR
incresed BFlow to adrenal
what controls ACTH release?
CRH stimulates ACTH release by corticotrophs
how does CRH stimulate ACTH release?
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
how does vasopressin affect CRH in response to stress?
it is synergistic by activating PLC to cleave PIP2 into DAG and IP3 to increase Ca levels
explain the neg feedback loop of cortisol release
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
what is the circadian pattern of cortisol release?
diurnal: levels highest in the morning and lowest after falling asleep
*8am corisol levels clinically b/c they elevate when you wake up
what does hypoglycemia stimulate?
it is a form of stress thus stimulates release of cortisol
what does it mean to be permissive?
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
how is cortisol permissive on the syn of glucagon?
it induces the activity of glucagon synthase thus having a permissive effect on glucagon and Epi induced glycogenolysis
what are the 2 biological actions of cortisol?
both permissive and synergistic (the combined effect of 2 hormones is greater than the sum of their individual effects)
how does cortisol protect against hypoglycemia?
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
do circulating levels of cortisol rise during a fast?
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
how does cortisol effect fat metabolism
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.
how does cortisol increase body fat content?
through an effect on appetite and by indirectly stimulating release of insulin
how does cortisol affect proteins and peptides involved in mediating inflammation? what action allows for inflammation to occur?
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
besides blocking NFkappaB, how else does cortisol suppres inflammation?
induce syn of anti-inflam IL-10 and lipocortin
lipocortin inhibits phospholipase A2 thus preventing arachidonic acid to cleave into leukotrienes and prostaglandins
what are the 9 overall actions of cortisol?
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
how is cortisol immunosuppressive?
decrease circulating levels of lymphocytes and eosinophils
induces apoptosis in immature lymphocytes thus decrease size of lymphatic tissues
inhibit syn of cytokines
excessive use of synthetic glucocorticoids puts pt at risk for what?
developing osteoporosis b/c corisol inhibits Ca uptake by intestine, Ca reabsorption by kidney, bone forming activity of osteoblasts
primary adrenocortical insufficiency AKA?
Addisons disease-defect w/n adrenal gland by Tb, tumor, autoimmune disorder**
what are the 5 cardinal signs of Adrenal insufficiency?
1. weakness-cortisol def
2. hyperpigmentation-excessive ACTH
3. hypotension-lack of aldosterone
4. nausea and vomiting
5. vitiligo
ACTH ___ pigmentation?
increases b/c POMC cleaved to ACTH which induces expression of pigment thus hyperpigmented in Addison's disease
what are the aldosterone consequences of adrenal insufficiency ?
decreased renal reaborption of Na = hyponatremia, depletion of total body Na, polyuria
extracellular fluid depletion-hypotension, dehydration
what are the cortisol consequences of adrenal insufficiency ?
inability to handle stress
hypoglycemia when strssed
decreased appetite
hyperpigmentation caused by excessive ACTH secretion
GI discomfort
what is secondary adrenocortical insufficiency caused by? compared w/ primary?
insufficient prodxn of ACTH by pituitary LOW ACTH
*pituitary H is the problem

primary: adrenal gland itself is destroyed thus HIGH ACTH
what is the result of long Tx with synthetic glucosteroids?
ACTH will decrease b/c corisol levels rise
adrenal could atrophy
thus keep stress low b/c could become hypoglycemic
what is happening in Cushings syndrome?
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)
what are some impot clinical features of Cushing's?
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
Primary hyperaldosteronism is AKA?
conn's syndrome
most common cause of primary hyperaldosteronism? symptoms?
Conn's syndrome: adenoma of zona glomerulosa
cause of secondary hyperaldosteronism?
inappropirate activation of renin-aldosterone system (renin secreting tumor)
congenital adrenal hyperplasia deficiecies are transmitted?
what happens with a CAH with mutation in 21hydroxylase?
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
what is a common feature of CAH?
defect in syn of cortisol leading to rise inACTH and hyperplasia of adrenal
why is a boy with CAH taller than his brother?
incrase sex steroids stimulates the release of GH
what is the only source of circulating epinephrine
adrenal medulla
what cells secrtete catecholamines?
chromaffin cells of adrenal medulla that are postganglionic cells w/ no axons
what is the rate limiting step in cat synthesis?
the first step: conversion of tyrosine to DOPA by tyrosine hydroxlase
waht is dopamine converted to and where? how does it enter?
dopamine converted to NE in chromafin granule
dopamine enters granule by VMAT (vesicular monoamine transporter) that is a cat-H exchanger
to become epi, what must NE do?
leave chromafin granule to enter cytoplasm where PMNT converts it to Epi
epi then enters granule via VMAT where it is stored
where are cats stored?
in chromaffin granulesin a complex with ATP, Ca and water soluble proteins called chromogranins**
where does most of Epi and NE come froem?
Epi:all from adrenal medulla
NE: 70% from nerve terminals
how is the syn of cats inhibited?
feedback inhibited :cats inhibit tyrosine hydroxylase
how is the adrenal medulla activated?
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
effect of cortisol on cats?
induces PMNT to convert NE to Epi
how are cats released?
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
which of the cats protect against hypoglycemia?
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
what 4 hormones fight hypoglycemia?
1. GH
2. glucagon
3. Epi
4. cortisol
principal enyzmes of cat degradation?
MAO monoamine oxidase **in neuronal tissues
COMT cat O methyltransferase *in non-neuronal tissues
what is the prinicpal degradative cat enzyme in Neuronal tissue? non-neuronal?
neuronal: MAO
non: COMT
what are the end products of cat breakdown?
vanillylmandelic acid
both conjugated and excreted in urine
the actions of cats are mediated by?
adrenergic R's
alpha 1/2
beta 1/2
mxn of action of alpha 1 adrendergic R?
increase IP2 and DAG
mxn of action of alpha 2 adrenergic R?
decrease cAMP
mxn of action of beta 1/2 adrendergic r's
increase cAMP
what is a pheochromocytoma?
cat producing tumor of chromaffin cells of the adrnal medulla
most freq released: NE
what secretory product of thyroid follicles represents 90% of thyroid output?
thyroxine (T4) while T3 represents only 10% of thyroid output
80% of T3 is derived from where?
what is rT3?
less than 1% output
biologically inactive
an enlarged thyroid gland is called a ?
goiter: goiter does NOT describe the fxnl state of the thyoid
where is TG?
colloid of thyroid follicle
where is the iodide pump involved in iodide trapping/
basolateral surface and is driven by the Na gradient of the Na/K atpase
iodide pump: 2 Na in/ i I in
where is TG released upon exocytosis? into where?
exocytosed from apical surface of cell into must be iodinated as it enters colloid ..the Iodide pump is located on basolateral surface
what can inhibit the iodide pump?
percholate (HCLO4) **competes with I for pendrin channel
how can one asscess the capacity of the thyroid to take up iodide?
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
what is the pendrin?
iodide channel located on apical surface that allows pumped in I to exit thryoid cells into follicular lumen
how much of the circulating pool of I is normally extracted?
the iodination of tyrosyl residues of TG is called what? when does it occur?
occurs as TG is extruded into follicular lumen
one monoiodinotyrosine peptide combines w/ diiodotyrosine to form what?
T3 triiodotryosine
what is the enzyme that iodinates TG to form MIT and DIT?
thyroid peroxidase
what are the 3 inhibitors of I uptake?
HClO4 (percholate)
TcO4 (pertechnetate)
CNS- (thiocyanate)
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
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)
75% of thryoid H is bound to?
thyroxine binding globulin
circulating levels are greater for T4 or T3? why
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?
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?
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?
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 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
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?
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?
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
is the PAR inactivated during X chromosome inactivation?
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?
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
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?
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?
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?
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?
*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?
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?
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?
waht is the size of the preantral follicle as it begins to grow? waht does it consist of?
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?
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?
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?
thyrotrophs in ant pituitary produce waht?
Lactotrophs in ant pituitary produce waht?
Corticotrophs in ant pituitary release what?
insulin growth factor (IGF-2) is present mostly in?
GH acts on liver to produce waht?
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?
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)
what is requd for gene expression of GH besides GH?
pituirtary transcription factor (Pit-1)
what are the 2 hormones that regulate GH?
SS -
what must happen when GH binds to target cells?
cross linking of 2 receptors
what actions of GH are mediated by IGF's?
all growth stimulating hormones (not metabolic actions)
IGF itself may act in endocrine, paracrine, and autocrine manner
in the tissuees, GH action is mediated by _____ IGF-1
locally produced IGF-1 and therefore GH activity may not at all be related to the circulating level of IGF or GH
waht does IGF compete for ?
insulin R
explain the differences b/n insulin and IGF's
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
when is IGF biologically active? what do they bind to?
only the FREE IGF
bind to tyrosine-kinase R's with cross reactivity in binding
which agents other than GH stimulate IGF prodxn in bone?
sex steroids
in reproductive system, IGF is produced from?
produced locally from sex steroids
what happens to GH during stress?
GH is reduced
what factors decresae GH?
undernutrition/fasting/ starving which cause decrease IGF, IGF R's which leads to catabolic actions
Trauma: GH decrease, IGF decresae
pre puberty excess GH is called wht? post puberty?
pre: gigantism
post: acromegaly
what are the metabolic affects of excess GH?
constant increase in blood sugar
incresaed insulin leading to Type 2 diabetes
more muscle-atherosclerosis
excess of what hormone will give you high fasting glucose concentrations, hi insulin secretion but resistance to insulin action?
excess GH
cells in the periventricular region release what? neurosecretory cells in arcuate nucleus?
SS, inhibitor of GH
arcuate: GHRH
net affect depends on the ratio
IGF inhibits ___ secretion?
what is the main stress that INCREASES GH? (all other stress decreases GH)
acute hypoglycemic stress
this is b/c GH raises glucose
what is the affect of exercise on GH?
exercise stimulates GH increase which stimulates prodxn of IGF therefore good vascular development which leads to less ischemia
waht is pituitary dwarfism?
pituitary failure of GH prodxn and consequent proportional redxn in body size
what is Laron syndrome:
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
compare levels of GH in GH defienciy v/s GH insensitivity?
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
direct action of GH?
direct: incresae plasma glucose, stimulate lipolysis, decrease peripheral glucose uptake
indirect: by IGF's and are ANABOLIC: IGF increase cartilage syn in epiphyseal plates
during puberty, increased androgen secretion increases waht?
GH secretion
what steroids are produced in pituitary?
NONE..only peptides and glycoproteins
waht are considered pituitary glycoprpotein hormones? what are they composed of?
composed of 2 subunits: alpha and beta but beta is unique to each hormone
action of FSH in males? females?
males: stimulates sertoli cells to begin spermatogenesis
femles: increse E2 in follicles leading to ovualation
action of LH in males? females?
males: stimulate Leydig cells to secrete testosterone
females: increase E2 for ovulation, progesterone
differnt gonadotropins pulse at differnt freq. a faster pulse gives you? slower?
faster: LH
slower: FSH
what affect does excess PRL have on GnRH? how does this affect the gonads?
decreaes GnRH b/c neg feedback
leads to hypogonadism in both men and women
if you have hyperprolactinemia where does teh problem lie?
with dopamine not being delivered, made,etc
pituitary tumor
anti-dopaminergic therapy medications
affect of stress on PRL?
stress causes PRL secretion
low ACTH causes?
Addison's syndrome, hyponatremia
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)
prolactin is secreted in the absence of exogenous stimuli
suppressed by dopamine from hypothalamus
what is luteinization?
after ovulation, LH promotes teh differentiation of follicular cells into luteal cells to form corpus luteum
fxn of corpus luteum?
produces hormones that favor implantation of an ovum: estrogens and progesterone *mainly progesterone is incresed in luteal phase
what controls the steroid syn of corpus luteum?
LH: a drop in LH will cause a rapid decline in hormone prdxn by the corpus luteum
waht is the life time of the corpus luteum
constant: lenght of luteal stage = 13-14 days
what hormone maintains the corpus luteum in nonpregnanct adult?
what inhibin is associated wiht follicular phase? luteal?
follicular: B produced by granulosa cells
luteal: A formed by corpus luteum
waht is a good indicator of granulosa fxn? corpus luteum fxn?
inhibin B levels during follicular phase
inhibin A to assess LH mediated corpus luteum fxn
how does the prodxn of estrogen affect the granulosa cells?
acts synergistically with FSH to promote granulosa cell proliferation
why do FSH and estrogen promote LH R' biosyn?
so that granulosa cells of maturing follicle become sensitive to LH
when do granulosa cells begin to acquire LH receptors?
mid follicular phase as they prepare for LH surge
waht hormone midcycle stimulates GnRH freq?
estradiol to pos feedbac for LH surge
prolferative phase of endometrial cycle is analogous to what ovary stage? what is the dominant hormone of poliferative phase?
follicular which begins with the onset of menses
estrogen is dominant hormone which causes the increase in endometrium
secretory endometrial phase is analogous to what ovarian phase? main hormones?
luteal phase
both estrogen and progesterone from corpus luteum which is regulated by LH
release of what caues the endometrium to involute in menstrual phase? (also causes "cramps")
prostaglandin PGF2a: causes vssls to become spastic and induces uterine contractions
what is menopause?
when all fxnl follices are depleted
age 45-55
cessation of menstruation
decline in estrogen levels
what is the predominant srum estrogen after menopause? where does this come from?
derived from peripheral conversion of androgens formed from fat
what are the clinical manifestastions of menopause? caused by?
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
when is the fertilit period?
2 days before and 1 day after ovultion (ovum only viable 1 day after ovulation)
at the end of the follicular stage, what is the consistency of the cervial mucus?
watery to make it possible for sperm to transit the cervical canal
where does fertilization occur?
in the ampula of fallopian tube
steps of fertilization
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
what happens after sperm enters the cells?
1. completion of 2nd meitosis of oocyte
2. cortical rxn: hardening of zone pellucida to keep others out
fertilization dominated by __ H
implantation dominated by ___ H
ferti: estrogen
implantation: progesterone
what hormone decreases constriction allowing Morula (solid ball of cells) to move down oviduct?
what is the portion of cells that penetrate the endometrium?
syncytiotrophoblast: begin to form placenta
once the blastocyst implants, the stroma forms what?? what are the changes involved?
increased edema
storage of nutrients in stromal cells
what maintains the endocrine secretion by the placenta?
it is autonomous..not regulated by maternal or fetal signals
what hormone sustains the corpus luteum for placenta to form?
similar to LH in structure
secreted by trophoblast cells
long T1/2
fxn: prolong life of corpus luteum and stimulate testosterone prodxn by fetus
what is the major hormone during pregnancy? produced by?
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
action of chorionic somatomammotropin (hCS)?
placental lactogen
acts like prolactin
antagonizes teh actions of insulin
effct of estrogens on breast development?
promote growth and branching of duct system in the presence of progesterone
waht are the 4 hormones that are present for breast develpment during pregnancy?
prolactin: lobuloalveolar development/promotion of milk secretion
human placental lactogen: same as PRL
3 hormones that have a permissive effect on brest development?
what prevents you from lactating during pregnancy?
estrogen and progesterone levels
(estrogen sits in prolactin R blocking action)
following parturition, what is the most potent stimulus for PRL release?
why after birth do we have a drop in prl?
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
the principal mxn of PRl action is activation of what pathway?