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Block 3: Pituitary Hormones

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Name 4 important drugs to know from this section
Somatropin
Bromocriptine
Cabergoline
Octreotide
Hormones (+) or (-) second messeger systems and involve intracellular [?] of
cyclic AMP
Ca2+
Activation of kinases
What are the hormones that enter cells called? Where do they bind?
Steroids

Receptors on the cell membrane
Do steroids cause the immediate secretion of hormones?
No, they regulate the rate of transcription and translation
3 categories of hormones
Steroids
Peptides
Amines
The major steroids
Adrenal
Sex
Calciferols
The major peptides
Hypothalamic releasing factors

Pituitary hormones

Insulin and Glucagon

Calcitonin

Oxytocin, vasopressin, relaxin

GI hormones

Angiotensin
The major amines
dopamine
epinephrine
thyroid hormone
How are peptides and catecholamines administered?
Steroids?
1. Must be parenterally
2. can be oral
Negative feedback and examples
Release of substrate (-) release of hormone

Glucagon/insulin
PTH/plasma Ca
Aldosterone/plasma Na
Glugagon/glucose
Example of complex endocrine control
Hypothalamic-ant. pituitary control of endocrine gland~ ea. step controlled by different hormone
Examples of hormones with complex control
TRH/TSH
CRH/ACTH/glucocorticoids
GnRH/LH
FH/estrogen and progesterone
Stucture of hGH (Somatotropin)
191 a.a.
Actions of Somatotropin
+ nitrogen balance (cell takes in more N than it puts out) w/increased protein syn.

Na, K, Ca, P, and Cl retention
Difference between hGH and insulin
GH favors fat as primary sourse of energy, insulin favor sugars
hGH and diabetics
hGH has diabetic effect (favors fat metab, not sugar) causing hyperglycemia and ketosis in diabetics (only).
How do they think GH acts predominantely
Release of somatomedin C (IGF-1) in growth plates and liver
Fxn of somatomedin C
Acts on chondrocytes to stimulate cartilage replication and formation
Does somatomedin C stimulate fat metab. like hGH?
No
What hormone caues hGH secretion? Which (-) secretion?
1. GHRH (predominant regulator)

2. Somatostatin (SST)
How do GHRH and Somatostatin (SST) work?
Alter adenyl cyclase
GHRH cascade
Binds to receptor attached to Gs, activates adneyl cyclase, converts ATP to cAMP, activates kinase, phosphorylates proteins, enhancement of GH synthesis and release
SST cascade
Binds receptor, attached to Gi, (-) adenyl cyclase and Ca2+ channels--- inhibits GH release
Factors that stimulate GH release
Hypoglycemia
Oral or i.v. amino acids (esp. arginine)
Deep sleep
Exercise
Dopamine agonists
Main treatment for hypopituitary dwarfism
GH or GHRH
Problem w/using glucocorticoids to suppress immune fxn in children
Also supresses GH, leads to retarded growth rate and bone age. May never reach full height
Why did they stop giving hGH extracted from cadavers?
3 people contracted Creutzfeldt-Jakob dz
What does recombinant hGH look like? How is it administered?
Identical (191 aa)

0.1mg/kg 3X/wk or
0.05 mg/kg/day
s.c. or i.m. injection
Can GHRH be synthesized?
Yes
*they first isolated it from pancreatic tumors
Laron syndrome. Possible treatment
Hyperpituitary dwarfism- defective GH receptors

Somatomedin C
Why has GH been called the fountain of youth?
Increases muscle mass
Reduces body fat
Reduces wrinkling
Woo hoo!!!
What may GH shots increase the risk of?
Carpel Tunnel Syndrome
What is acromegaly? Major cause?
Hypersecretion of GH in an adult

Pituitary adenoma often Gs is constantly activated
Why use bromocriptine to treat acromegaly? Why is this weird?
This DA agonist parodoxically (-) GH secretion in 50% of pts. w/acromegaly. Normally bromocriptin increase release of GH
Pts. who respond to bromcriptine usually have what?
Tumors that secrete GH and Prl.
New D2 receptor agonist effective in decreasing GH levels
Cabergoline
Why can't we use SST to treat acromegaly? Alternative?
Metabolized too quickly

Octreotide- synthetic SST analog that has longer 1/2 life
Administration of octreotide?
Side effects
i.m. injection once/month

Diarrhea, nausea, abdominal pain (50%)
What else does SST inhibit?
ACTH, TSH, insulin, glucagon, VIP*
Octreotide can also be called...and used to treat...
Sandostain

Pancreatic cholera due to xs VIP secretion
Problem w/long term treatment of VIP tumors with Octreotide
Tumors become resistant
Prl works in concert with what?
Thyroxine, sex, and adrenal steroids.
What is the predominant regulator of lactotrophs in the ant. pituitary.
DA, binds to D2 receptor on lactotroph
Where in the pituitary is DA released?
Median eminence
What enhances the release of Prl? How?
TRH
Formation of IP3 to increase intracellular Ca2+
How does DA work on lactotrophs?
binds D2 receptor, activates Gi, (-) adenyl cyclase, opens K and closes Ca channels
Prolactin secretion in increased by
(7)
Pregnancy
Suckling
Psychic and physical stress
Hypoglycemia
High dose estrogen
DA receptor blockers (chlorpromazine (thorazine), haloperidol)
Drugs that deplete DA: reserpine, alpha methyldopa
Prl secretion inhibited by...
DA agonists: l-dopa, bromocriptine, Cabergoline
Problems from hyperprolactinemia?
Galactorrhea, ammenorrhea
compression of the optic nerve (bromocriptine makes tumors shrink)
When is it safe to take a pt. off thier DA agonist when being treated for hyperprolactinemia?
Never, tumors recur

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