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252 Cards in this Set
- Front
- Back
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Protien and peptide hormone syntheis
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1. preprohormone is synthesized in the ER
2. signal peptides are cleaved from the preprohormone -> prpohormone, which is transported to the Golgi 3. Additional cleavate in the Golgi results in the hormone -> packaged into secretory granules |
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list the amine hormones
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- thyroid hormone
- epinephrine - norepinephrine |
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what are amine hormones derivatives of?
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- tyrosine
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give an example of positive feedback
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- the surge of LH that occurs just before ovlulation is the result of postive feedback of estrogen on the ant. pituitary.
- LH acts on ovaries to cause more estrogen secretion |
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thyrotropin-releaseing hormone (TRH)
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- made in the hypothalamus
- stimulates THS and prolactin secretion |
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Corticotropin-releasing hormone (CRH)
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- made the in hypothalamus
- stimulates secretion of ACTH |
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Gonadotropin-releasing hormone (GnRH)
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- made in the hypothalamus
- stimulates secretion of LH and FSH |
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Growth hormone releasing hromone (GHRH)
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- made in hypothalamus
- stimulates GH secretion |
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Somatotropin release- inhibiting hormone (SRIF)
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- aka somatostatin
- made in hypothalamus - inhibits GH secretion |
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Prolactin-inhibiting factor (PIF)
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- aka dopamine
- made in hypothalamus - inhibits prolactin secretion |
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Thyroid-stimulating hormone (TSH)
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- made in ant. pituitary
- stimulates synthesis and secretion of TH |
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Follicle stimulating hormone (FSH)
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- made in ant. pituitary
- stimulates growth of ovarian follicles and estrogen secretion - promotes sperm maturation |
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Luteinizing hormone (LH)
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- made in ant. pituitary
- in ovaries: stimulates ovulation, formation of the corpus luteum, and synthesis of estrogen and progesterone - in testes: stimulate secretion and synthesis fo testosterone |
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Growth hormone (GH)
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- made in the ant. pituitary
- stimulates protein synthesis and overall growth |
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Prolactin
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- made in ant. pituitary
- stimulates milk production and breast development |
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Adrenocorticotropic hormone (ACTH)
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- made in ant. pituitary
- stimulates synthesis and secretion of adrenal cortical hormones |
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b- lipotropin
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- made in ant. pituitary
- unknown function in humans |
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Melanocyte stimulating hormone (MSH)
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- made in ant. pituitary
- stimulates melanin synthesis - unclear fcn in humans |
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Oxytocin
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- made in post. pituitary
- milk ejection - uterine contraction |
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Antidiuretic hormone (ADH)
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- aka vasopressin
- made in post. pituitary - stimulates H2O reabsoption in collecting ducts |
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L-thyroxine (T4)
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- made in thyroid gland
- promotes skeletal growth - increases O2 comsumption - increases heat production - increase protein, fat and carb use - maturation of nervous system (perinatal) |
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Triiodothyronine (T3)
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- made in thyroid gland
- promotes skeletal growth - increases O2 comsumption - increases heat production - increase protein, fat and carb use - maturation of nervous system (perinatal) |
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Glucocorticoids
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- aka cortisol
- made in adrenal cortex - stimulates gluconeogenesis - anti-inflammatory - immunosuppression |
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Estradiol
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- made in ovaries
- growth and developme tof female reproductive organs - follicular phase of menstrual cyce |
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Progesterone
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- made in ovaries
- luteal phase of menstrual cycle |
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Testosterone
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- made in testes
- spermatogenesis; male secondary sex characteristics |
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Parathyroid hormone (PTH)
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- made in parathyroid gland
- increase serum [Ca] and decrease serum [phosphate] |
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Calcitonin
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- made in thyroid gland (parafollicular cells)
- decrease serum [Ca] |
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Aldosterone
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- made in adrenal cortex
- increase renal Na reabsorption - increase renal K secretion - increase renal H secretion |
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1, 25 dihydroxycholecalciferol
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- activated in the kidney
- increase intestinal Ca absorption - increase bone mineralization |
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Insulin
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- made in pancreas beta-cells
- decrease blood glucose - decrease blood FFA - decrease blood amino acids |
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Glucagon
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- made in pancreas alpha-cells
- increase blood glucose - increase blood FFA |
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Human chorionic gonadotropin (HCG)
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- made by the placenta
- increase estrogen and progesterone synthesis by corpus luteum |
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Human placental lactogen (HPL)
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- made by the placenta
- stimulates proteins synthesis and overall growth (GF) - formation of the corpus luteum, and synthesis of estrogen and progesterone (like LH) |
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how does progesterone act on receptor regulation?
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- down-regulates its own receptor, and the receptor for estrogen
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how does estrogen act on receptor regulation?
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- in the ovary, estrogen up-regulates it own receptor and the receptor for LH
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name the three 2nd messanger systems that use G-proteins
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1. adenylate cyclase
2. Ca-calmodulin 3. inositol 1,4,5-triphophate (IP3) |
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what are the three subunits of G proteins?
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- alpha, beta, gamma
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name a phosphodiesterase inhibitor
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caffeine
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anterior pituitary
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- is linked to the hypothalamus by the hypothalamic-hypophysial portal system
- blood from hypothalamus with hormones is delivered to ant. pituitary |
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posterior pituitary
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- derived from neural tissue
- nerve cell bodies are fond in the HYPOTHALAMIC NUCLEI - post. pituitary hormones are synthesized in the nerve cell bodies, and packaged into secretory granules -> transported down the axons to the post. pituitary |
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name the hormones of the anterior pituitary
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1. GH
2. prolactin 3. TSH 4. LH 5. FSH 6. ACTH (please love girl FAT) |
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which ant. pituitary hormones belong to the same glycoprotein family?
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- TSH, LH, FSH
- composed of an a subunit and a b subunit - a subunits are identical among the three hormones. - the b subunit is different and is responsible for the biologic activity of each hormone |
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which hormones of the ant. pituitary are derived from the same precursor?
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- ACTH, MSH, b-lipotropin and b-endorphin
- all derived from POMC - a-MSH and b-MSH are made in the intermediatary lobe, which is rudimentary in adults |
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what is another name for growth hormone?
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- somatotropin
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describe the structure of GH
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- single chain polypeptide that is HOMOLOGOUS WITH PROLACTIN and human placental lactogen
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describe the regulation of GH secretion
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- pulsatile secretion
- secretion increased by sleep, stress, puberty hormones, starvation, exercise, hypoglycemia - secretion decreased by somatostatin, somatomedins, obesity, hyperglycemia, pregnancy |
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describe the hypothalamic control of GH
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- GHRH stimulates synthesis/secretion of GH
- somatostatin inhibits synthesis/secretion of GH by blocking the response of the ant. pit to GHRH |
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describe the neg feedback control of GH by somatomedins
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- somatomedins are made when GH acts on target tissues
- somatomedins inhibit secretion of GH by 1. acting on ant. pit, and 2. causing hypothalamus to secrete somatostatin |
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describe the neg feedback control of GH by GHRH and GH
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- GHRH inhibits its own secretion from the hypothalamus
- GH inhibtis its own secretion by stimulating somatostatin release from the hypothalamus |
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what does GH do to the liver?
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- generates production of somatomedins (insulin-like growth factors (IGF)), which serve as intermediaries fo several physiologic actions
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describe the IGF receptor
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- has tyrosine kinase activity, similar to the insuilin receptor
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list the direct actions of GH
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1. decrase glucose uptake into cells (diabetogenic)
2. increase lypolysis 3. increase protein synthesis in muscle and increase lean body mass 4. increase production of IGF |
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list the actions of GH via IGF
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- increase protein synthesis in chrondrocytes and increase LINEAR GROWTH (pubertal growth spurt)
- increase protein synthesis in muscle and increase lean body mass - increase protein synthesis in most organs and increases organ size |
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what happens with GH deficiency?
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- failure to grow, short stature, obesity, delayed puberty
- caused by: - lack of ant. pit GH - hypothalamic dysfunction (decreased GHRH) - failure to generate IGF in the liver - GH receptor deficiency |
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what happens with GH excess?
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- can be treated with somatosatin analogs -> inhibit GH secretion
- will cause acromegaly - before puberty -> linear growth (gigantism) - after puberty -> increased periosteal bone growth, increased organ size, glucose intolerance |
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what is the main hormone responsible for lactogenesis?
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prolactin
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name a somatostatin analog
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octreotide
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what does prolactin do?
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- lactogenesis
- breast development (when acting along with estrogen) - inhibits ovulation by decreasing synthesis/relase of GnRH - inhibits spermatogenesis (decrease GnRH) |
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describe the structure of prolactin
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- homologous to GH
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describe the hypothalamic control of prolactin secretion
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- controled by DA and thyrotropin-releasing hormone (TRH)
- prolactin secretion is tonically inhibited by DA (prolactin inhibitng factor (PIF) secreted by the hypothalamus - interruptino of the hypothalamic-pit tract causes increased secretion of prolactin and sustained lactation - TRH increases prolactin secretion |
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describe the negative feedback control of prolactin
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- prolactin inhibits its own secetion by stimulating the hypothalamic release of DA
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what happens with prolactin deficiency?
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- caused by destruction of the ant. pit
- failure to lactate |
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what happens with prolactin excess?
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- cuased by hypothalamic destriction from loss of tonic inhibitory control by DA, or from prolactin-secreting tumors (prolactinomas)
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what are prolactinomas?
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- prolactin secreting tumors
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what does prolactin excess cause?
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- galactorrhea and decreased libido
- failure to ovulate and amenorrhea b/c of inhibited GnRH secretion |
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how do you treat prolactin excess?
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- bromocriptine, which reduces prolactin secretion by acting as a DA agonist
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bromocriptine
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reduces prolactin secretion by acting as a DA agonist
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name the hormones of the posterior lobe of the pituitary
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1. ADH
2. Oxytocin - homologous nonapeptides - synthesized in hypothalamic nuclei - packaged in secretory granules with their respective neurophysins - travel down the axon for secretion by the post. pit |
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define neurophysin
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any of a group of soluble proteins secreted in the hypothalamus that serve as binding proteins for vasopressin and oxytocin, playing a role in their transport in the neurohypophyseal tract and their storage in the posterior pituitary.
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where is ADH made?
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- in the supraoptic nuclei of the hypothalamus
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which factors increase ADH secretion?
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- increased serum osmolarity
- volume contraction - pain - nausea - hypoglycemia - nicotines, opiates, antineoplastic drugs |
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actions of ADH on principal cells
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1. increase H2O permeability of principal cells of the late DT and CD
- V2 receptor and adenylate cyclase -cAMP mechanism |
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actions of ADH on vasculature
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- constriction of vascular smooth muslce
- V1 receptor and IP3/Ca2+ mech |
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where is oxytocin produced?
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- paraventricular nuclei of the hypothalamus
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what does oxytocin do? how is it regulated?
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- causes ejection of milk
- stimulated by suckling (or sometimes even just sight and sound of a baby) - increased by dilation of the cervix and orgasm |
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what does oxytocin do?
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- contraction of myoepithelial cells in the breast
- contraction of uterus - oxytocin receptors are up-regulated in the uterus during pregnancy - can be used to INDUCE LABOR AND REDUCE POSTPARTUM BLEEDING |
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list the steps to TH sythesis
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* each step is stimulated by TSH
1. Thyroglobulin is synthesized from tyrosine 2. I- pump, or Na-I cotransport 3. Oxidation of I- to I2 4. Organification of I2 5. Coupling of MIT and DIT 6. Stimulation of thyroid cells by TSH 7. Binding of T3 and T4 8. Conversion of T4 to T3 and reverse T3 |
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where is TH synthesized? TG?
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- in the thyroid follicular cells
- TG is synthesized from tyrosine, packed into secretory vesicles, and extruded into the follicular lumen |
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what inhibits the iodide pump, or Na-I cotransport in the thyroid follicular cells?
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- thiocyanate
- percholorate anions |
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what inhibits the peroxidase enzyme?
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- propylthiouracil
- used therapeutically to treat hyperthyrodism |
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propylthiouracil
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- inhibts peroxidase enzyme to prevent TH synthesis
- treats hyperthyroidism |
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what is teh Wolff-Chaikoff effect?
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- having high levels of I- so that organification (I2 combined with tyrosine on TG to form MIT and DIT) is impaired
- inhibits synthesis of TH |
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how do you synthesize I3? I4?
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- DIT + MIT -> I3
- DIT + DIT -> I4 |
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which is synthesized in higher levels? T3 or T4?
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- T4 is syntheized more
- T3 however, is more active |
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what happens when the thyroid gland is stimulated by TSH?
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- iodinated TG is taken back into the follicular cells by endocytosis
- lysosomal enzymes digest the TG -> relase T3 and T4 into the circulation |
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what happens to left over MIT and DIT?
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- deiodinated by thyroid deiodinase
- deficiency in deiodinase mimics I2 deficiency b/c the I2 that is released after breakdown of I3 and I4 is used to make more TH |
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what binds T3 and T4 in circulation?
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- thyroxine-binding globulin (TBG)
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what happens to TH levels with hepatic failure?
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- TGB levels decrease -> decrease in total TH levels, but a normal level of free hormone
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what happens to TH levels in pregnancy?
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- TGB levels increase -> increase in total TH, but normal levels of free hormone
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what happens to T4 in peripheral tissues?
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- converted to T3 (or rT3) by 5'-iodinase
- T3 is more active than T4 - rT3 is inactive |
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describe the regulation of TH secretion
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- TRH is secreted by the hypothalamus -> stimulates TSH secretion by the ant. pit
- TSH increases synthesis AND secretion of TH by the follicular cells by the cAMP mech) - T3 down-regulats TRH receptors in the ant pit -> inhibits TSH secretion |
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Grave's disease
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- high levels of IgG antibodies to TSH receptors on the thyroid gland -> over stimulation of the thyroid gland to secrete T3 and T4
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what serum values do you see in Grave's disease
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- high levels of TH
- low concentrations of TSH |
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what is the potency of T3 compared to T4?
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- T3 is 4x more potent than T4
- target tissues convert T4 to T3 and rT3 |
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what does TH do?
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- growth
- acts synergistically with GH and somatomedins to promote bone formation - stimulate bone maturation as a result of ossificatoin and fusion of growth plates |
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what do you see in the bones of patients with TH deficiency?
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- bone age is less than chronologic age
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what does TH do on the CNS?
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- perinatal period: maturation of the CNS
- TH deficiency causes metal retardation - adulthood: hyperthyroidism, hypothyrodism |
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describe hyper and hypo thyroidism
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- hyper: hyperexcitability and irritability
- hypo: listlessness, slowed speech, somnolence, impaired memory, decreased mental capacity |
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what does TH do on the ANS?
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- same action as the sympathetic NS
- up regulates B1 receptors in the heart - useful adjunct therapy for hyperthyroidism is b-adrenergic blocker like propranolol |
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what do you want to give in a hyperthyroid patient for thier heart?
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- B- adrenergic blocking agent bc TH causes upregulated B1 receptors in the heart
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what does TH do to BMR?
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- increase BMR and O2 consumption in all tissues except brain, gonads, and spleen -> increase in heat production
- increase synthesis of Na, K, ATPase and increases O2 consumption related to Na-K pump activity |
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what does TH do to the cardio and respiratory systems?
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- increase CO, HR, and RR to ensure that more O2 is delivered to tissues
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what dose TH do to metabolism?
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- increased
- glucose absorption from GI tract is increased - glycogenolysis, gluconeogenesis, and glucose oxidation are increased - lipolysis is increased - protein synthesis and degredation is increased - overall effect: CATABOLIC |
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what symptoms do you see with hyperthyrodism?
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- increase met rate
- weight loss - neg nitrogen balance - increased heat production - increased CO - dyspnea - tremor, weakness, exophthalmos - goiter |
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how do you treat hyperthyroidism?
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- propylthiouracil
- thyroidectomy - 131- I - B-blockers (adjunct therapy) |
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what causes hyperthyrodism?
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- graves'disease
- thyroid neoplasm |
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what are the symptoms of hypothyroidism?
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- decreased BMR
- weight gain - positive nitrogen balance - decreased heat production (cold sensitivity) - decreased CO - hypoventilation, lethargy - drooping eyelids, myxedema - goiter |
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what causes hypothyroidism?
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- thyroiditis (autoimmune, Hashimoto)
- Surgical removal - I- deficiency - Cretinism - decreased TRH or TSH |
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what does the zona glomerulosa make?
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- aldosterone
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what does the zona fasiculata make?
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- glucocorticoids (cortisol)
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what does the zona reticlaris make?
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- androgens (dehydroepiandosterone and androstenedione)
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name the 21- carbon steroids
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- progesterone, deoxycorticosterone, aldosterone, cortisol
- progesterone is the precursor for the other 21 carbon series - hydroxylation at C-21 leads to production fo deoxycorticosterone - hydroxylation at C-17 leadst o production of glucocorticoids (cortisol) |
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describe deoxycorticosterone
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- formed by the hydroxylation of progesterone at C-21
- has minerolocorticoid, but not glucocorticoid, activity |
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name the 19-carbon steroids
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- have androgenic activity
- the precursors to the estrogens - if the steroid has been previously hydroxylated at C-17, the C20,21 side chain can be cleaved to yield the 19-carbon steroids: dehydroepiandrosterone or androstenedione in the adrenal cortex |
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also under 19-carbon steroids
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- adrenal androgens have a ketone group at C-17 and are excreted as 17-ketosteroids in the urine
- in the testes, androstenedione is converted to testosterone |
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describe the 18-carbon steroids
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- have estrogenic activity
- oxidation of the A ring (aromatization) to produce estrogens occurs n the ovaries and placenta, but not in the adrenal cortex or testes |
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describe the cyclicity of glucocorticoid secretion
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- oscillates with a 24 hour periodicity (circadian rhythm)
- cortisol levels are highest just before waking (~8am) and lowest in evening (~12 midnight) |
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describe the hypothalamic control - Corticotropin-releasing hormone (CRH) of glucocorticoid secretion
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- CRH-containing neurons release CRH into the hypothalamic-
hypophysial portal blood when stimulated, and delivers CRH to the ant. pit - CRH binds to receptors on corticotrophs of the ant. pit and causes them to synthesize POMC and secrete ACTH |
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what is the second messanger for CRH?
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- cAMP
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where are CRH-containing neurons found?
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- paraventricular nuclei of the hypothalamus
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describe the ant pit- ACTH control of glucocorticoid secretion
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- ACTH increases steroid hormone synthesis in all zones of the adrenal cortex by stimulating CHOLESTEROL DESMOLASE and by increasing the conversion of cholesterol to pregnenolone
- ACTH up-reg its own receptor -> increase sensitivity of the cortex to ACTH |
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what happens with chronically increased levels of ACTH?
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- causes hypertrophy of the adrenal cortex
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what is the second messanger for ACTH?
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- cAMP
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describe the negative feedback control of glucocorticoid secretion (cortisol)
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- cortisol inhibits secretion of CRH from the hypothalaus and secretion of ACTH from the ant pit
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what is the dexamethasone suppression test?
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- ability of dexamethasone (synthetic glucocorticoid) to inhibit ACTH secretion
- in persons with ACTH secreting tumors, low-dose dexamethasone doesn't inhibit cortisol secretion, but high dose does - in adrenal cortical tumors, neither low or high dose dexa methasone can inhibit cortisol secretion |
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describe what controls aldosterone secretion
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- under tonic control by ACTH
- separately regulated by the renin-angiotensin-aldosterone system - hyperkalemia increases aldosterone secretion since aldosterone increases renal K secretion |
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list the actions of glucocorticoids (cortisol)
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- essential for the stress response
1. stimulation of gluconeogenesis 2. anti-inflammatory effects 3. suppression of the immune system 4. maintenance of vascular responsiveness to catecholamines |
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describe the stimulation of gluconeogenesis caused by glucocorticoids
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- glucocorticoids increase protein catabolism in muscle and decrease prothein synthesis -> more amino acids available for gluconeogeneis
- decrease glucose utilization and insulin sensitivity of adipose tissue - increase lipolysis -> more glycerol for liver to use for gluconeogenesis |
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describe the anti-inflammatory effects exerted by glucocorticoids
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- induce synthesis of lipocortin -> inhibts phospholipase A2
- reduced prostaglandin and leukotriene levels - inhibit production of IL-2 and proliferation of T cells - inhibit release of histamine and serotonin from mast cells and platelets |
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lipocortin
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- inhibitor of phopholipase A2
- induced by glucocorticoids |
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phospholipase A2
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- enzyme that liberates arachidonate from membrane phosphlipids, proiding the precursor for prostaglandin and leukotriene synthesis
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describe the suprression of the immune response by glucocorticoids
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- inhibitthe production of IL-2 and T cells
- glucocorticoids are used to prevent rejection of transplanted organs |
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describe the maintenance of vascular responsiveness to catecholamines
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- cortisol up regulates a1 receptors on arterioles -> increased sensitivity to vasoconstrictor effects of NE
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what happens to BP with cortisol excess?
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- arterial pressures increase b/c of upregulated a1 receptors on vasculature
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what does aldosterone do?
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- increase renal Na absorption (acts via the principal cells)
- increase renal K secretion (acts on the principal cells) - increase renal H secretion (acts on the a-intercalated cells) |
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how can you get adrenocortical insufficiency?
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1. Primary adrenocortical insufficiency (Addison's disease)
2. Secondary adrenocortical insufficiency |
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Addison's disease
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- autoimmune destruction of the adrenal cortex -> acute adrenal crisis
- decreased adrenal glucocorticoid, androgen, and mineralocorticoid - increased ACTH - hypoglycemia (from cortisol def) - weight loss, weakness, nausea, vomiting - hyperpigmentation (increased ACTH has MSH fragment) - decreased pubic and axillary hair in women (decreased androgens) - ECF volume contraction, hypotension, hyperkalemia, met acidosis (from aldosterone def) |
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describe secondary adrenocortical insufficiency
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- caused by primary deficiency in ACTH
- does not have hyperpigmentation - no volume contraction, hyperkalemia, or metabolic acidosis b/c ACTH levels are normal - symptoms otherwise similar to Addisons' disease |
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Adrenocortical excess- Cushing's syndrome
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- mainly caused by CVS
- also caused by primary hyperplasia of adrenal glands - Cushing's disease: overproduction of ACTH |
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describe what you see in Cushing's syndrome
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- increased cortisol and androgen
- decreased ACTH (if primary; decreased if Cushing's disease) - hyperglycemia (from high cortisol) - increased protein catabolism - central obesity - poor wound healing - verilization of women - hypertension, osteoporosis, striae |
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what does cortisol do on bone?
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- increased bone resorption
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ketoconazole
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- inhibitor of steroid hormone synthesis
- treats Cushing's disease |
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Hyperaldosteronism- Conn's syndrome
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- caused by aldosterone secreting tumor
- hypertension - hypokalemia - metabolic alkalosis - decreased renin (kidney senses increased ECF and BP) |
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how do you treat Cushing's syndrome?
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- ketoconazole
- Metyrapone |
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how do you treat Conn's syndrome?
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- Spironolactone (aldosterone antagonist)
- surgical removal of aldosterone secreting tumor |
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21B-hydroxylase deficiency (general)
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- most common biochemical abnormality in the steroidogenic pathway
- belongs to a group of disorders characterized by the adrenogenital syndrome |
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21B- hydroxylase deficiency (symptoms)
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- decreased cortisol and aldosterone
- increased 17-hydroxyprogesterone and progesterone levels (accumulation of intermediates) - increased ACTH (decreased feedback inhibition by CORTISOL) - hyperplasia of zona fasciculata and reticularis (ACTH) - increased adrenal androgens, increased urinary 17-ketosteroids - virilization in women, early linear growth and pubic hair - suppression of gonadal fcn |
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what is the precursor for aldosterone?
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- 11- deoxycorticosterone
- synthesis to aldosterone is blocked by 21B-hydroxylase deficiency |
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what is the precursor for cortisol?
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- 11 deoxycortisol
- synthesis to cortisol is blocked by 21B-hydroxylase deficiency |
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17a-hydroxylase deficiency
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- decreased androgen and glucocorticoid levels
- increased mineralocorticoid levels - lack of pubic and axillary hair in women - hypoglycemia - met. alkalosis, hypokalemia, hypertension - increased ACTH (decreased cortisol) |
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list the three cell types in islets of Langerhans. How are they connected?
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1. Beta
2. Alpha 3. Delta - gap junctions link beta and alpha cells - the portal blood supply allows blood from the beta cells (with insulin) to bathe the alpha and delta cells, for rapid cell-to-cell communication |
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what are the islets of Langerhans cells?
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endocrine producing cells in the pancreas
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where are beta cells found?
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- central islet
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where are alpha cells found?
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- secrete glucagon
- outer rim of islet |
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where are delta cells found?
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- intermixed in the islet
- secrete somatostatin and gastrin |
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what is the mech of insulin?
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- tyrosine kinase receptor
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what is the mech of glucagon?
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- cAMP
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what does CCK do?
|
- cholecystokinin
- increase lipolysis and ketoacid production - increases fatty acid and ketoacid levels in the blood - glucagon stimulates its secretion |
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what does GIP do?
|
- Glucose-dependent insulinotropic peptide
- increase protein synthesis - decreases amino acid levels in the blood - insulin stimulates its secretion |
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how does glucagon increase gluconeogenesis?
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- decreases the production of fructose 2,6 bisphosphate -> decreases phosphofructokinase activity
|
|
|
how does glucagon increase blood fatty acid and ketoacid concentrations?
|
- increases lipolysis
- ketoacids (b-hydroxybutyrate and acetoacetate) are produced from acetyl CoA, which results from fatty acid degredation |
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|
name two major ketoacids
|
- b-hydroxybutyrate
- acetoacetate |
|
|
list the actions of glucagon
|
1. increase blood glucose concentration
2. increase blood fatty acid and ketoacid 3. increase urea production |
|
|
how does glucagon increase urea production?
|
- amino acids are used for gluconeogenesis
- resulting amino groups are incorporated into urea |
|
|
describe the structure of insulin
|
- A chain and B chain, joined by two disulfide bridges
- proinsulin is synthesized as a single-chain peptide - in storage granules, a connecting peptide (C-peptide) is removed to produce insulin - C peptide is secreted along with insulin - [C peptide] is used to measure beta cell function in diabetics recieving exogenous insulin |
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|
how do you determine B cell function in patients receiving exogenous insulin?
|
- look for C peptide concentrations
|
|
|
how does the beta cell respond to insulin?
|
- insulin binds to the Glut 2 receptor on beta cells
- inside the beta cells, glucose is oxidized to ATP, which closes K channels -> depolarization -> opening of Ca cannels -> increase in intracellular Ca -> insulin |
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|
how do sulfonylrea drugs work?
|
- tolbutamide and glyburide stimulate insulin secretion by closing the K channels -> depolarization -> opens Ca channels -> increase in intracellular Ca -> secretion of insulin
|
|
|
tolbutamide
|
- sulfonylurea drug
- pumps the beta cells - causes closure of K channels |
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|
glyburide
|
- sulfonylurea drug
- pumps beta cells - closes K channels |
|
|
describe the insulin receptor
|
- tetramer (2a and 2beta subunits)
- B subunit spans the cell membrane; has tyrosine kinase activity - when insulin binds receptor, TK autophosphorylates the B subunits -> phosphorylates intracellular proteins - insulin receptor complex ENTERS the cell |
|
|
what are factors that promote insulin secretion?
|
- GIP
- ACh - fatty acids - glucagon - amino acids - blood glucose |
|
|
what are factors that decrease insulin secretion?
|
- decreased blood glucose
- somatostatin - NE, Epi |
|
|
describe insulin receptor regulation
|
- insulin down-regulates its receptors in target tissues
- increased receptors in starvation - decreased receptors in obesity |
|
|
how does insulin decrease gluconeogenesis?
|
- increases the production of fructose 2,6 bisphosphate -> increase phosphofructokinase activity
|
|
|
how does insulin affect serum K?
|
- increases K uptake into cells -> decreases blood K
- (remember insulin's action on beta cells!) |
|
|
why would a diabetic have high amino acid and fatty acid levels in the blood?
|
- increased protein catabolism
- increased lipolysis - body thinks its starving |
|
|
why would a diabetic have hypotension?
|
- high glucose load exceeds the reabsorptive capacity (T_m) of the kidney
- the glucose that is excreted acts as a osmotic diuretic |
|
|
what is somatostatin? what does it do?
|
- secreted by the delta cells of the pancreas
- inhibits secretion of insulin, glucagon, and gastrin |
|
|
describe overall Ca homeostasis
|
- 40% of total Ca in blood is bound to plasma proteins
- 60% is not bound, and is ultrafilterable - ultrafilterable Ca includes Ca that is complexed to anions (e.g. phosphate) and free Ca2+ - free, ionized Ca is biologically active |
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|
when do you see a positive Ca balance? neg balance?
|
- pos: in growing children
- neg: in women during pregnancy or lactation; deficit comes from maternal bones |
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|
what is the major hormone for serum Ca regulation?
|
- parathyroid hormone
|
|
|
where is parathyroid hormone (PTH) made?
|
- chief cells in the parathyroid glands
|
|
|
describe the regulation of PTH secretion
|
- controled by serum Ca by neg feedback
- mild decreases in serum Mg stimulates PTH secretion - severe decreases in serum Mg inhibits PTH secretion -> hypoparathyroidism |
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|
what is the second messanger for PTH secretion by the chief cells of the parathyroid gland?
|
- cAMP
|
|
|
describe the actions of PTH
|
- produces increase in serum Ca and decrease in serum phosphate
- increases bone resorption - inhibits renal phosphate reabsorption in the PT - increases renal Ca reabsorption in DT - increases intestinal Ca absorption |
|
|
what is the second messanger for PTH actions on its target tissues?
|
- cAMP
|
|
|
describe the effect PTH has on bone resorption
|
- increases bone resorption -> increases serum levels of Ca and phospahte
- does not increase free Ca, since phosphate complexes Ca - instead, you'll see increased hydroxyproline excretion |
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|
describe the effect PTH has on renal phosphate
|
- inhibits reabsorption in the PT -> increased excretion (phosphaturic effect)
- allows serum free ionized Ca to increase - cAMP generated as a result of PTH on the PT is excreted as urinary cAMP |
|
|
how does PTH increase intestinal Ca absorption?
|
- indirectly, by stimulating production of 1,25 dihydroxycholecalciferol in the kidney
|
|
|
list the disorders of PTH
|
1. primary hyperparathyroidism
2. humoral hypercalcemia of malignancy 3. hypoparathyroidism 4. Pseudohypoparathyroidism type Ia- Albright's hereditary osteodystrophy 5. Chronic renal failure |
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|
Primary hyperparathyroidism
|
- caused by parathyroid adenoma
- hypercalcemia - hypophosphatemia - phosphaturic effect of PTH (increased urinary excretion of phosphate) - increases urinary Ca excretion - urinary cAMP - bone resorption |
|
|
Humoral hypercalcemia of maligancy
|
- caused by PTH related peptide (PTH-rp) secreted by some malignant tumors
- PTH-rp has all the properties of PTH - hypercalcemia - hypophosphatemia - phosphaturic effect of PTH-rp * Decreased serum PTH levels (feedback inhibition from high serum Ca) |
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|
hypoparathyroidism
|
- caused by thyroid surgery, or congenital defect
- hypocalcemia and tetany - hyperphosphatemia - decreased urinary phosphate excretion |
|
|
Psuedohypoparathyroidism type Ia- Albright's hereditary osteodystrophy
|
- defective G_s protein in kidney and bone -> organ resistance to PTH
- hypocalcemia, and hyperphosphatemia - not correctable by administration of PTH - circulating PTH levels are elevated |
|
|
Chronic renal failure and PTH
|
- decreasd GFR -> decreased filtratin of phosphate -> phosphate retension -> increased serum phosphate -> decreased free Ca
* decreased production of 1,25-dihydroxycholecalciferol by diseased kidney -> decreased ionized Ca -> secondary hyperparathyroidism -> renal osteodystrophy : increased bone resorption and osteomalacia |
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|
define: osteomalacia
|
Also know as "adult rickets." A softening of the bones as a result of a deficiency of vitamin D or chronic renal failure
|
|
|
what does Vit D do? what does its deficiency cause?
|
- vit D provides Ca and phosphate to ECF for bone mineralization
- children: vit D def -> rickets - adults: vit D def -> osteomalacia |
|
|
name the inactive forms of Vit D
|
- cholecalciferol
- 25- hydroxycholecalciferol - 24,25 dihydroxycholecalciferol |
|
|
name the active form of Vit D
|
- 1,25 dihydroxycholecalciferol
|
|
|
what allows for the production of 1,25-dihydroxycholecalciferol
|
- catalyzed by a1-hydroxylase
- activity of this enzyme is increased by: - decreased serum Ca - increased PTH - decreased serum phosphate |
|
|
what are the actions of 1,25 dihydroxycholecalciferol?
|
- increases BOTH Ca and phosphate in ECF to mineralize new bone
- increases intestinal Ca absorption - increases intestinal phosphate absorption - increases renal reabsorption of Ca and phosphate - increases bone resorption: Ca and P are taken from old bone to make new bone |
|
|
describe how 1,25 Dihydroxycholecalciferl increases intestinal Ca absorption
|
- vit D dependent Ca binding protein calbindin D-28K) is induced by 1,25 dihydroxycholecalciferol
- PTH increase intestinal Ca absorption indirectly by stimulating 1a- hydroxylase and increasing prodcution of the active form of Vit D |
|
|
Calcitonin
|
- synthesized and secreted by the parafollicular cells of the thyroid
- stimulated by increase in serum Ca - inhibits bone resorption - treats hypercalcemia |
|
|
what is gonadal sex?
|
- testes in male
- ovaries in female |
|
|
what is phenotypic sex?
|
- internal genital tract and external genitalia
|
|
|
what is the male phenotype?
|
- testes of male secrete antimullerian hormone and testosterone
- testosterone stiulates growth of wolffian ducts -> become male internal genital tract - antimullerian hormone causes atrophy of the mullerian ducts |
|
|
what is the female phenotype?
|
- overaries secret estrogen, but not antimullerian hornome or testosterone
- without testosterone, wolffian ducts do not differentiate - without antimullerian hormone, mullerian ducts develop into internal genital tract |
|
|
synthesis of testosterone
|
- made by leydig cells
- LH inreases testosterone synthesis by stimulating cholesterol desmolase - accessory sex organs (prostate) contain 5a-reductase -> testosterone is converted to active form: dihydrotestosterone (DHT) |
|
|
why don't leydig cells make glucocorticoids or mineralocorticoids?
|
- don't contain 21B-hydroxylase or 11B-hydroxylase in contrast to the adrenal cortex
|
|
|
what enzyme converts testosterone to its active form?
|
- 5a-reductase converts testosterone to dihydrotestosterone
|
|
|
what is used to treat BPH (benign prostatic hypertrophy)?
|
- 5a-reducatase inhibitors (finasteride)
|
|
|
finasteride
|
- 5a reducatase inhibitor.
- used to treat BPH by blocking activation of testosterone to dihydrotestosterone in prostate |
|
|
list the three areas that control the testes
|
1. hypothalamic control: GnRH
2. Anterior pituitary: FSH and LH 3. Negative feedback control: testosterone and inhibin |
|
|
how does hypothalamic control (GnRH) affect the testes?
|
- the arcuate nuclei of the hypothalamus secrete GnRH into the hypothalamic hypophysial portal blood
- GnRH stimulates the ant pit to secrete FSH and LH |
|
|
how does the anterior pituitary (FSH and LH) affect the testes?
|
- FSH acts on Sertoli cells to maintain spermatogenesis
- Sertoli cells secrete inhibin - LH acts on Leydig cells -> testosterone synthesis - Testosterone acts via a intratesticular paracrine mech to reinforce the spermatogenic effects of FSH on Sertoli Cells |
|
|
how does testosterone exert neg feedback?
|
1. inhibits secretion of LH by inihibiting the release of GnRH from the hypothalamus and,
2. by directly inhibiting the release of LH from the ant. pit |
|
|
how does inhibin exert neg feedback
|
- Inhibin is produced by the Sertoli cells
- inhibits the secretion of FSH from the ant. pit |
|
|
what are the actions of testosterone
|
- differentiation of epididymis, vas deferens, seminal vesicles
- pubertal growth spurt - epiphyseal closure - libido - spermatogeneisis in Sertoli cells (paracrine effect) - increased muscle mass - growth of penis and seminary vesicles |
|
|
what are the actions of dihydrotestosterone?
|
- differentiation of penis, scrotum, prostate
- male hair pattern - male pattern baldness - sebaceous gland activity - growth of prostate (BPH) |
|
|
what is androgen insensitivity disorder?
|
- aka testicular feminizing syndrome
- caused by deficiency of androgen receptors - default female external genitalia and no internal genital tract - testosterone levels are elevated (no neg feedback) |
|
|
what is puberty initiated by?
|
- pulsatile GnRH release from the hypothalamus
- FSH and LH are, in turn, secreted in pulsatile fashion - GnRH up-regulates its own receptor in the ant. pit |
|
|
describe the variation in FSH and LH over the life span of males and females
|
- in childhood, hormone levels lowest: FSH > LH
- at puberty, hormone levels increase: LH > FSH - in senescence, hormone levels are highest: FSH > LH |
|
|
synthesis of estrogen and progesterone
|
- theca cells make testosterone (stimulated by LH)
- testosterone diffuses to granulosa cells, which contain aromatase and convert testosterone to 17B-estradiol (stimulated by FSH) |
|
|
how is the ovary regulated?
|
1. Hypothalamic control (GnRH)
2. Anterior lobe of pituitary (FSH and LH) 3. Neg and Pos feedback control: estrogen and progesterone |
|
|
how does the anterior pit regulate the ovary?
|
- FSH and LH stimulate the ovaries
- steroidogenesis of the ovarian follicle and corpus luteum - follicular development beyond the antral stage - ovulation - luteinization |
|
|
describe estrogen
|
- has both + and - feedback effects on FSH and LH
- causes maturation of fallopian tubes, uterus, cervix, and vag - causes secondry sex char - up-reg estrogen, LH and progesterone receptors - causes proliferation and development of granulosa cells |
|
|
what is the role of estrogen during pregnancy?
|
- maintains pregnancy
- lowers uterine threshold to contractile stimuli during pregnancy - stimulates prolactin secretion, but blocks its action on the breast |
|
|
what hormone exerts +/- control during the follicular phase?
|
estrogen
- neg feedback to the ant. pit |
|
|
what hormone exerts +/- control during the midcycle phase?
|
estrogen
- pos feedback to the ant. pit |
|
|
what hormone exerts +/- control during the luteal phase
|
estrogen: neg feedback to the ant. pit
Progesterone: neg. feedback to the hypothalamus |
|
|
describe progesterone actions
|
- neg feedback effects on FSH and LH during the luteal phase
- maintains secretory activity of the uterus during the luteal phase - maintains pregnancy - raises the uterine threshold to contractile stimuli during preg - participates in breast development |
|
|
what are the three phases in the menstrual cycle?
|
1. follicular phase (0-14)
2. Ovulation (14) 3. Luteal phase (14-28) |
|
|
describe the folliuclar phase
|
- primordial follicle develops to the graafian state
- atresia of neighboring follicles - LH and FSH receptors are up-reg in theca and granulosa cells - estradiol levels inrease -> proliferation of uterus - FSH and LH are suppressed by the neg feedback effect of estradiol on the ant. pit - progesterone levels low |
|
|
describe ovulation
|
- occurs 14 days before menses, regardless of the cycle length
- burst of estradiol at the end of the follicular phase -> pos feedback on secretion of FSH and LH -> LH surge -> ovulation due to LH surge - estrogen levels decrease just before ovulation, but rise in luteal phase |
|
|
describe the changes to cervical mucus
|
- increases in quantity during ovulation
- becomes less viscous and more penetrable by sperm |
|
|
describe the luteal phase
|
- corpus luteum begins to develop -> synthesizes estrogen and progesterone
- vascularity and secretory activity of endometrium increases - baseal body temp rises - if fertilization does not occur, corpus luteum regresses and there is a fall in estradiol and progesterone |
|
|
why does the basal body temp increase in the luteal phase?
|
- effect of progesterone on the hypothalamic thermoregulatory center
|
|
|
describe menses
|
- days 0-4
- endometrium is sloughed off b/c of abrupt withdrawl of estradiol and progesterone |
|
|
describe preganancy
|
- steadily increasing levels of estrogen and progesterone, which maintains the endometrium for the fetus and suppresses ovarian function by inhibiting LH and FSH secretion
- stimulates breast growth |
|
|
fertilization
|
- if fertilization occurs, the corpus luteum is rescued from regression by HCG, which is produced by the placenta
|
|
|
1st trimester
|
- corpus luteum, stimulated by HCG is responsible for the production of estradiol and progesterone
- peak levels of HCG occur at gestational week 9, and then go down |
|
|
2nd and 3rd trimesters
|
- progesterone is produced by placenta
- estrogens are produced by fetal adrenal galnd and the placenta - human placental lactogen is produced throughout pregnancy: has actions like GH and prolactin |
|
|
describe the role of the fetal adrenal gland
|
- makes DHEA-S, which is hydroxylated in the fetal liver
- the intermediates are transfered to the placenta, where enzymes remove sulfate and aromatize to estrogens |
|
|
what is the major placental estrogen?
|
- estriol
|
|
|
partrition
|
- progesterone increases during pregnancy to increase the threshold for uterine contraction
- near term, estrogen:progesterone ratio rises -> more likely to contract - initiating event in parturition is unknown |
|
|
how do you artifically stimulate uterine contraction?
|
- oxytocin
|
|
|
lactation
|
- estrogens and progesterones stimuate growth and development of breasts throughout pregnancy
- prolactin levels increase during pre b/c estrogen stimulates prolactin secretion from the ant pit |
|
|
why doesn't lactation occur during pregnancy?
|
- estrogen and progesterone block the action of prolactin on the breast
- after parturition, estrogen and progesterone levels drop -> lactation |
|
|
how is lactation maintained?
|
- suckling behavior
- stimulates oxytocin and prolactin |
|
|
how is ovulation supressed during lactation?
|
- prolactin:
- inhibits GnRH secretion -> inhibits LH and FSH secretion - antagonizes actions of LH and FSH on ovaries |
