Ant Pituitary Agents

Question 1

How is GH a metabolic hormone?

Answer 1

promotes lipolysis

counter-regulatory hormone to hypoglycemia and insulin - presents FFA to liver to make glucose

Question 2

What is the mechanism of GH/prolactin action?

Answer 2

binds receptor w/o kinase activity - recruits JAK2 kinase, activates and phosphorylates STAT5 –> promotes transcription of target genes like IGF-1

Question 3

What is Laron’s dwarfism?

Answer 3

mutations in GHR that completely inactivate it - completely resistant to GH but respond to IGF-1 therapy

Question 4

What does IGF-1 do?

Answer 4

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

Question 5

What are the positive and negative regulators of GH release?

Answer 5

positive - GHRH from arcuate nucleus regulates synthesis and release
negative - somatostatin, regulates timing of release, not synthesis

Question 6

What are two important facts about GH?

Answer 6

somatotropes most susceptible of ant pituitary to insult

GH def most common single ant pit hormone def

Question 7

What is the feedback regulation of GH?

Answer 7

IGF-1 inhibits at hypothalamus and ant pit

Question 8

What can stimulate GH secretion?

Answer 8

protein rich meal (Arg can stimulate pulse)
hypoglycemia
stress, exercise, sleep
alpha adrenergic agents
dopamine and seretonin

Question 9

What can inhibit GH secretion?

Answer 9

glucose load (basis for glucose tolerance test), fatty acids
beta adrenergic agents

Question 10

What can cause GH deficiency?

Answer 10

acquired: brain injury, inf, mass effect, iatrogenic

genetic

Question 11

How can you tell the difference between FTT and GH def in children?

Answer 11

GH def actually chubby - only linear growth impaired

Question 12

What are the signs of GH def in adults?

Answer 12

subtle, increased adiposity and decreased bone mass

Question 13

How can GH def be diagnosed?

Answer 13

measure IGF-1

provocative testing: arginine, clonidine, or insulin to see if secretion

Question 14

How can GH excess be diagnosed?

Answer 14

elevated serum IGF-1
oral glucose tolerance test - are levels suppressed?
MRI to look for pit adenoma

Question 15

What is the syndrome of prolactin def?

Answer 15

failure of lactation, otherwise no real syndrome

Question 16

What are common etiologies for hyperprolactinemia?

Answer 16

pregnancy, pit adenoma, pharmacological (anti-psychotic = dopa antagonists), primary hypothyroidism - excess TRH and spillover, PCOS

Question 17

What are the gonadotropins?

Answer 17

FSH, LH, hCG

share common alpha subunit but different beta

Question 18

What is the mechanism of action for the gonadotropins?

Answer 18

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

Question 19

What regulates gonadotropin secretion?

Answer 19

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

Question 20

What are the clinical uses of gonadotropins?

Answer 20

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

Question 21

What is gonadorelin?

Answer 21

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

Question 22

What are the indications for use of GnRH agonists?

Answer 22

central (GnRH dependent) precocious puberty - persistent stimulation down regulates
hormone dependent cancers
endometriosis and uterine fibroids = estrogen-dependent
fertility treatment - short-term therapy