Ant Pituitary Agents Flashcards
How is GH a metabolic hormone?
promotes lipolysis
counter-regulatory hormone to hypoglycemia and insulin - presents FFA to liver to make glucose
What is the mechanism of GH/prolactin action?
binds receptor w/o kinase activity - recruits JAK2 kinase, activates and phosphorylates STAT5 –> promotes transcription of target genes like IGF-1
What is Laron’s dwarfism?
mutations in GHR that completely inactivate it - completely resistant to GH but respond to IGF-1 therapy
What does IGF-1 do?
made in liver
can activate insulin receptor when high - lowers glucose levels
half life prolonged by IGFBP-3 and ALS - IGF-1 serum levels stable
What are the positive and negative regulators of GH release?
positive - GHRH from arcuate nucleus regulates synthesis and release
negative - somatostatin, regulates timing of release, not synthesis
What are two important facts about GH?
somatotropes most susceptible of ant pituitary to insult
GH def most common single ant pit hormone def
What is the feedback regulation of GH?
IGF-1 inhibits at hypothalamus and ant pit
What can stimulate GH secretion?
protein rich meal (Arg can stimulate pulse) hypoglycemia stress, exercise, sleep alpha adrenergic agents dopamine and seretonin
What can inhibit GH secretion?
glucose load (basis for glucose tolerance test), fatty acids beta adrenergic agents
What can cause GH deficiency?
acquired: brain injury, inf, mass effect, iatrogenic
genetic
How can you tell the difference between FTT and GH def in children?
GH def actually chubby - only linear growth impaired
What are the signs of GH def in adults?
subtle, increased adiposity and decreased bone mass
How can GH def be diagnosed?
measure IGF-1
provocative testing: arginine, clonidine, or insulin to see if secretion
How can GH excess be diagnosed?
elevated serum IGF-1
oral glucose tolerance test - are levels suppressed?
MRI to look for pit adenoma
What is the syndrome of prolactin def?
failure of lactation, otherwise no real syndrome
What are common etiologies for hyperprolactinemia?
pregnancy, pit adenoma, pharmacological (anti-psychotic = dopa antagonists), primary hypothyroidism - excess TRH and spillover, PCOS
What are the gonadotropins?
FSH, LH, hCG
share common alpha subunit but different beta
What is the mechanism of action for the gonadotropins?
act through GPCR that uses Gs
LH and hCG use same LH receptor
FSH and LH bind to receptors on gonads to regulate steroid and gamete production
What regulates gonadotropin secretion?
GnRH from hypothalamus promote - pulsatile*
constant GnRH delivery down regulates GnRH receptor and secretion lowered
gonadal steroids feedback to inhibit
estrogen has rare positive feedback at specific stage of menstrual cycle
inhibin inhibits FSH secretion
What are the clinical uses of gonadotropins?
hCG: pregnancy test, maybe tumor marker
LH: urine level can detect surge - helps timing for fertilization
FSH and LH: evaluate child for precocious/delayed puberty
can treat infertility
What is gonadorelin?
synthetic GnRH
used diagnostically to differentiate b/w GnRH independent or dependent precocious puberty
can also be used to stimulate release in women with hypogonadotropic hypogonadism
What are the indications for use of GnRH agonists?
central (GnRH dependent) precocious puberty - persistent stimulation down regulates
hormone dependent cancers
endometriosis and uterine fibroids = estrogen-dependent
fertility treatment - short-term therapy
