Intro to Reproductive Axis Flashcards
Control of Anterior pituitary hormone release
Release of hypothalamic hormones under CNS control via NTs
Release of anterior pituitary hormones (trophic hormones) controlled by hypothalamic hormones.
-Then delivered via portal circulation to the pituitary gland for release into the sytemic circ where they act on endocrine glands to regulate production of hormones that perform ultimate regulatory functions.
Control of posterior pituitary hormone release
Synthesized in peptidergic neurons in the hypothalamus and then transported to the neuronal terminal in the posterior lobe of pituitary
Neuronally released into the systemic circulation and act directly on target tissues to perform regulatory functions
Growth hormone (pharm analogs)
Somatropin Somatrem (no longer available) t1/2 25 mins IM peak 2-4 hrs Active levels persist 36 hrs
Pharmacodynamics of GH
-release increased by GHRH, exercise, hypoglycemia, dopamine, L-DOPA, arginine
Decreased by somatostatin
At pharm doses, GH works indirectly to stimulate synthesis of insulin like growth factors (IGF-1, IGF-2) promoting linear and skel muscle growth
GH replacement therapy in kids
Daily at bedtime via SC injection (more effective, mimics natural release pattern) or 3 times a week IM
What if kid is growth hormone insensitive?
- can treat with recombinant IGF-1
- concern with hypoglycemia (take carbs before)
Uses of GH (FDA approved)
-poor growth from Turner’s syndrome, Prader-Willi syndrome, and chronic renal insufficiency
Growth hormone deficiency in adults (pit tumor)
Treatment of wasting or cachexia in AIDS patients
Patients with short bowel syndrome dependent on total parenteral nutrition
Illicit uses of GH
-athletes to increase muscle mass, improve performance (lack of evidence)
-healthy adults for “anti-aging” effects
small changes in body composition and increased rates of adverse events
off label use is ILLLEGAL
Side effects of GH (somatropin)
-generally safe for kids
-insulin resistance and glucose intolerance may occur
-Slight increased risk for idiopathic intracranial hypertension (pseudotumor cerebri)
-Rarely pancreatitis, gynecomastia, nevus growth
•Misuse in athletes: Acromegaly, arthropathy, visceromegaly, extremity enlargement
GHRH
Rapidly stimulates GH synthesis and secretion via binding to GPCR coupled to Gs
-Note: Ghrelin stimulate GH release via a different GPCR
- Dominant inhibitory regulator is Somatostatin
- GH also acts as own feedback inhibitor.
GHRH analogs
Sermorelin (not on market)
Tesamorelin for HIV pts
Somatostatin
- Inhibits GH release via GPCR Gi decreasin cAMP levels, activating K+ channels
- reduces insulin and glucagon release
- interferes with TRH ability to release TSH
Somatostatin and analogs pharmacokinetics
Somatostatin: t1/2 3-4 mins limiting usefulness
Octreotide: t/12 90mins, SC every 6-12 h
Octreotide (Somatostatin LAR depot): IM every 4 weeks
Lanreotide given SQ every 4 weeks
Uses of Somatostatin analogs
Pituitary: excess GH
-acromegaly
-gigantism
But for adenoma: surgical resection preferred
-For pharm, though, long acting somatostatin analog is preferred
-Dopamine agonists may inhibit GH secretion in some pts. Cabergoline as adjuvant therapy for acromegaly (oral)
-GH receptor antag: Pegvisomant (SQ dose daily)
Non Pituitary:
Control of bleeding from esophageal varices and GI hemorrhage (constrict splanchnic arterioles)
Dopamine agonists
- inhibition of GH secretion (Cabergoline)
- hyperprolactinemia (decreases secretion and tumor size with D2 agonist)
