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29 Cards in this Set

  • Front
  • Back
How are hypothalamic hormones released and regulated?
released in a rhythmic/circadian pattern and regulated in a negative feedback loop.
What are the hormones released from the hypothalamus?
TRH; CRH; GnRH; GHRH; somatostatin; dopamine
What are the hormones released from the anterior pituitary that are stimulated by the hypothalamus?
What target organs and hormones are stimulated by the anterior pituitary?
Thyroxine & T3 from thyroid
glucocorticoid from adrenals
androgens, estrogens & progestins from gonads
IGF-1 from liver
what is the function of somatostatin?
To inhibit GH release from the anterior pituitary.
what is the function of dopamine?
Inhibits prolactin release.
Growth Hormone production
most abundant hormone in AP.
1 gene produces a heterogenous mix of peptides, leads to several GH's of different AA combos.
Growth Hormone control and release
controlled Somatostatin and GHRH
Released by nurons in hypothalamus in pulsatile fashion therfore pulsatile stimulation of somatrophs in AP which release GH.
Somatostatin receptors
there are up to 5 SS receptors: SSTR2 and SSTR5 are the most important
Decapeptide, inhibits GH, made in hypothalamus and pancreatic islets, also inhibits TSH, gonadotropins, insulin and glucagon release
GH Regulation
Negative Feedback loop
short loop- GH feedback to neurons of GnRH, inhibits GHRH's release
classic loop- end hormone (IGF-1)inhibits GH release of GHRH release
What influences GH secretion?
sleep, hypoglucemia, physical exertion, emotional excitement, drugs: increased by alpha agonists, L-dopa and amphetamines; decreased by Beta agonists and phenothiazines
What is the insulin tolerance test?
hypoclycemia increases GH release. Test: infuse insulin, blood gluc should dec, GH should inc, and cortisol should inc.
pharmocodynamics of GH
GH binds to cell surface receptors, and also circulates bound to extracellular protein domain of GH receptors
Function of GH alone
GH directly increases lipolysis and gluconeogenesis
Function of GH through IGF-1
anabolic and growth promoting effects (metab of proteins, fat, carbs, Ca) results in growth(increased cell number not size)
Function of IGF's
mediate most GH effects
IGF-2 activates intracellular mannose-6-phosphate receptor
IGF-1 binds receptors similar to insulin receptor
Diseases of hypo GH secretion.
dwarfism- in children
endocrinopathies in adults (including increased cardiovascular mortalities)
Diseases of hyper GH secretion.
Gigantism- in kids before epiphyseal plates close
acromegaly- after plates close
symptoms of acromegaly
visual problems from pituitary adenomas, bone overegrowth in hands, feet and face, headaches, sweating, diabetes, joint problems, colon cancer, cardiovascular disease
structurally related to GH
secretion influenced by same factors as GH plus estrogen
role= lactation
receptors on other cells have unknown functions
suppresses HPG-axis through actions on hypothalamus and gonads
Treatment= dopamine, bromocriptine, pergolide, cabergoline
SS analog,treats acromegaly, preferred because most specific for GH system, has modified Amino acid therefore longer t1/2 & greater selectivity,also used for metastatic carcinoid cancers, VIP secreting tumors, AIDS related diarrhea; SIDE EFFECTS: hypothyroidism, GI symptoms (loose stool, malabsorption, nausea and flatulence)
GH receptor antagonist, genetically engineered analog of human GH conjugated to polyethylene glycol= pegylation (reduces renal clearance and gives longer t1/2)
mech: blocks GH binding to receptor therefore decreases serum IGF-1 secretion but increases GH in serum
most effective for acromegegaly
SE: can develop auto GH Ab's leads to CV probs
dopamine agonist, treats acromegaly, hyperprolactinemia, amenorrhea, galactoffhea, infertility, hypogonadism, parkinson's; SE= HA, dizziness, nausea, HTN, postural hypotension, contraindicated in pts with sensitivity to ergot alkaloids
Growth Hormone as a drug
for dwarfism, chronic renal insufficiency, Turner's syndrome; can be prepared as hGH (somatropin)(encapsulated for monthly IM injections)or synthetic hGH with methionine removed (somatotrem)
inhibits prolactin release
for hyperprolactinemia,
longer t1/2, more potent D2 selective, used once or twice a week
preferred over bromcriptine in acromegaly