Monday - Pituitary phys and pharm - Trachte Flashcards
What 2 hormones regulate Growth Hormone (somatotropin) release
Growth Hormone releaseing Hormone (GHRH)
Growth Hormone Inhibiting Hormone (GHIH) = somatostatin. Uses Gi receptors –> K channels activated
Also, Dopamine inhibits GH
How does GHRH work?
G protein S
Adenylyl cyclase –> increase cAMP –> release GH
How is growth hormone transported?
bound to GH binding protein, which is a part of the receptor that has been cleaved off. how efficient.
What kind of intracellular signaling does the GH receptor use?
tyrosine kinase –> dimerization –> JAK/STAT –> activation of things in nucleus for metabolism, growth, proliferation and differentiation.
(TYRannOSaurus is large (GH))
What hormone has the same effects as GH
Insulin-like Growth Factor-1 (IGF-1, somatomedin)
What does GH do to each of these? Sodium insulin sensitivity fat stores protein synthesis epiphysial growth
Sodium --> retention insulin sensitivity --> decrease fat stores --> lipolysis protein synthesis --> promotes epiphysial growth --> obviously promotes
also increases IGF-1 production
In what ways to GH and IGF-1 oppose each other?
GH - decreases insulin sensitivity, but IGF-1 has insulin activity
GH - lipolysis
IGF-1 –> anti-lipolysis
Why did Barry Bonds need to get a bigger helmet?
Because he’s a cheater. (he took growth hormone) better put an asterisk by all his stats, am I right?
What happens to carbohydrate metabolism in response to GH
body decreases carb utilization, decreases uptake –> increases level in blood –> secondary release of insulin.
increases fats being used for energy
Laron Syndrome
GH receptor insensitive to GH - very short, but resistant to diabetes and cancers
low IGF-1 levels too
Proportional Dwarfism is due to what?
decreased GH in kids. Can be from Laron syndrome Turner Syndrome SHOX mutation poor nutrition stress
Symptoms of GH deficiency
obesity (reduced muscle mass)
reduced energy, weakness
reduced cardiac output
Why is it not super useful to measure levels of GH
it changes to much (pulsate pattern)
increases during sleep
IGF-1 is slightly better at measuring GH
A way to asses the GH activity using blood sugar levels
inject insulin –> hypoglycemia
GH should be released after this to increase glucose level in blood
Analog of GHRH called?
Sermorelin
Way to measure production of GH
collect baseline level of GH and IGF-1
inject Arginine
inject GHRH
measure GH over and hour
Side effects of giving GH
antibodies to it (its a protein)
Scoliosis
Diabetes
Recombinant Human IGF-1 is called?
Use?
Mecasermin
If GH receptor is bad (Laron Syndrome), can induce some growth. Fewer side effects than GH
Too much secretion of GH leads to:
Acromegaly
Diagnosis of GH hypersecretion
elevated IGF-1
Elevated GH 2 hrs after glucose
Treatment for GH hypersecretion
Somatostatin (octreotide) and dopamine (specifically the D2 receptor) (Bromocriptide)
Growth hormone antagonist used to treat acromegaly
Pegvisomant
can have liver tox and antibodies to it
Regulation of prolactin
Positive
- Prolactin releasing hormone (trachte doesn’t believe it exists)
- VIP
- Thyrotropin releasing hormone (TRH)
inhibitory
- Dopamine
How does the prolactin receptor work?
prolactin binds to receptor –> dimerizes –> tyrosine Kinase –> Jak/Stat –> trascriptional events
Effects of Prolactin
Breast development during pregnancy (lobular development)
Milk secretion during lactation (inhibited by progesterone)
What does the hypothalamus tonically do to prolactin levels
inhibits via dopamine (prolactin inhibitory hormone PIH)
D2 receptor
If infundibulum is severed, prolactin increases. others decrease
Also, no negative feedback when it’s released
What would lead to prolactin hypersecretion?
Prolactin secreting tumor
Tumor that disrupts inhibition
Dopamine blocking agents
Injury to infundibulum
Girl. no period. She’s lactating all over the place. Doesn’t have kids tho.
What’s wrong with her?
You may argue, nothing!
But she for sure has prolactin hypersecretion.
Treatment of prolactin secreting tumor
Dopamine (D2) agonist (bromocriptine. cabergoline has fewer side effects)
