Block 3: Pituitary Hormones
Terms
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- Name 4 important drugs to know from this section
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Somatropin
Bromocriptine
Cabergoline
Octreotide - Hormones (+) or (-) second messeger systems and involve intracellular [?] of
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cyclic AMP
Ca2+
Activation of kinases - What are the hormones that enter cells called? Where do they bind?
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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
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Steroids
Peptides
Amines - The major steroids
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Adrenal
Sex
Calciferols - The major peptides
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Hypothalamic releasing factors
Pituitary hormones
Insulin and Glucagon
Calcitonin
Oxytocin, vasopressin, relaxin
GI hormones
Angiotensin - The major amines
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dopamine
epinephrine
thyroid hormone -
How are peptides and catecholamines administered?
Steroids? -
1. Must be parenterally
2. can be oral - Negative feedback and examples
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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
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TRH/TSH
CRH/ACTH/glucocorticoids
GnRH/LH
FH/estrogen and progesterone - Stucture of hGH (Somatotropin)
- 191 a.a.
- Actions of Somatotropin
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+ 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?
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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
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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?
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Identical (191 aa)
0.1mg/kg 3X/wk or
0.05 mg/kg/day
s.c. or i.m. injection - Can GHRH be synthesized?
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Yes
*they first isolated it from pancreatic tumors - Laron syndrome. Possible treatment
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Hyperpituitary dwarfism- defective GH receptors
Somatomedin C - Why has GH been called the fountain of youth?
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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?
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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?
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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...
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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?
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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
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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?
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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