Hypothalmic and Pituitary Hormones Flashcards
hormones released from the posterior pituitary
ADH
Oxytocin
another name for growth hormone
somatotrophin
how does GHRH (growth hormone releasing hormone) stimulate the release of GH
GHRH binds to its receptor which couples with Gs protein causing an increasing in cAMP and Ca2+ –> GH synthesis and secretion
what inhibits secretion of GH and mechanism
- GH: via somatostatin (SST) by binding to Gi and causing a decrease in cAMP
- IGF-1: acts directly on the anterior pituitary inhibiting release of GH
things that stimulate the release of GH
- Dopamine, 5-HT, and alpha 2 receptor agonist
- hypoglycemia
- stress
- emotional excitement
- protein rich meals
things that inhibit release of GH (other than GH and IGF-1)
Beta agonists
Free Fatty acids
mechanism of interaction of GH with its receptor
- GH interacts with two identical receptors forming a ligand occupied receptor dimer
- Dimer provides docking site for two molecules of JAK2
- This lead to trans phosphorylation and auto-activation of JAK2
- Also there is tyrosine phosphorylation of cytoplasmic proteins that mediates downstream signaling events
- These include STAT proteins, SHC, IRS-1 and IRS-2
positive physiological effects of GH
- causes longitudinal growth in children
- increases bone density in adults
- increased muscle mass
- increase GFR
- stimulates preadipocytes to adipocytes
negative (used loosely) effects of GH
- anti insulin effects (esp in liver and peripheral sites such as adipocytes and muscle) –> hyperinsulinemia
- increases lipolysis
- stimulates gluconeogenesis
what happens with patients who are given IGF-1 due to being GH resistant
IGF-1 has pro-insulin effect –> hypoglycemia
physiological effects of those who are GH deficient
- they fail to reach their predicted adult height
- experience hypoglycemia due to unopposed effect of insulin (since lack of anti insulin GH)
- low lean body mass
what glucose transporters does GH inhibit
GLUT-1 and GLUT-4 (adipose tissue and muscle)
what are the two forms of GH that are used in GH deficient children
Somatotrophin (recombinant form, identical to human GH)
Somatrem (derivative of GH with additional methionine at the amino terminus)
Other than GH deficiency, what other conditions is GH used to treat
- wasting in AIDS patient
- Short Bowel Syndrome in those receiving specialized nutritional support
used to treat IGF-1 deficiency
Mecasermin (IGF-1 analogue)
adverse effect of Mecasermin
hypoglycemia
side effects of GH in children
HI VIP
- Headache
- Increased incidence of Type 2 DM
- Visual changes
- Intracranial hypertension
- Papilledema
side effects of GH in adults
CAMP
- Carpal tunnel Syndrome
- Arthralgia
- Myalgia
- Peripheral Edema
who is GH contraindicated in
active malignancy
what does GH excess cause
- if epiphyseal hasn’t sealed, increased longitudinal growth –> gigantism
- in adults –> acromegaly
what is used to treat GH excess
- Somatostatin analogues
- Dopamine agonists
- GH receptor antagonist
what is the somatostatin analogue and what is its mechanism
Octreotide is TIGGG
Octreotide - inhibits release of TSH, Insulin, GH, Glucagon, and Gastrin
adverse effect of GH in Turner Syndrome
Otitis Media
clinical application of Octreotide
- Reduce the release of TIGGG –> TSH, Insulin, Gastrin, GH, and Glucagon
- Secretory Diarrhea
- Bleeding in esophageal varices
adverse effects of Octreotide
- Constipation
- Gallstones
if dopamine agonist stimulate the release of GH, how then does it decrease GH secretion
it somehow paradoxically does, and best works in patients whose tumors secrete GH and prolactin
what are the dopamine agonists and what else can they be used to treat
Bromocriptine and Cabergoline —> both have high affinity for dopamine D2 receptors
used to treat hyperprolactinemia (dopamine inhibits prolactin release)
side effects of dopamine agonists (name them)
bromocriptine and cabergoline
nausea, vomiting, headache, postural hypotension
what is the GH receptor antagonist and its use
mechanism
Pegvisomant - treatment of acromegaly
binds GH receptor –> does not activate JAK/STAT pathway or IGF-1 secretion
use of prolactin and way to decrease it secretion if prolactinoma
- produces milk
- give dopamine receptor agonists, surgery, radiation
what are the gonadotrophic hormones and what stimulates their release
FSH, LH, hCG –> stimulated by release of GnRH from hypothalamus
why is long acting GnRH used to suppress gonadotropic secretions
continuous secretion of GnRH –> desensitization and downregulation of GnRH receptors on pituitary
it need to be secreted in pulses
what is the synthetic GnRH and the GnRH analogues
synthetic naive GnRH: Gonadorelin
GnRH analogues: Leuprolide, Goserelin, and Nafarelin
side effects of synthetic GnRH and its analogues
hot flashes sweating headaches decreased bone density gynecomastia in males
major drawback to using long acting GnRH analogues
at first, transient increase in sex hormone levels before lasting suppression of hormone synthesis and secretion
Gonadorelin can be used to clinically treat what
short acting and if used in pulsatile fashion –> stimulates patterned gonadotropin release
used to treat female and male infertility related to hypothalmic hypogonadotropic hypogonadism and for diagnosis of LH responsiveness
GnRH competitive receptor antagonist and mechanism
Ganirelix
Cetrorelix
inhibit secretion of FSH and LH
why would GnRH competitive receptor antagonist be used in metastatic prostate cancer (name them)
Ganirelix and Cetrorelix
avoids initial surge of testosterone caused by treatment with GnRH agonists
what is estrogen and progesterone under the control of? what takes over during pregnancy
under control of LH
hCG takes over during pregnancy
