pit2


Growth hormone-releasing hormone (GHRH) (+) ® growth hormone {somatotropin, GH)®Liver ® insulin-like growth factors (IGF, somatomedins)
Somatotropin releasing-inhibiting hormone (SRIH, somatostatin) (-) ® growth hormone {somatotropin, GH)®Liver ® insulin-like growth factors (IGF, somatomedins)
Corticotropin-releasing hormone (CRH) (+) ® adrenocorticotropin (ACTH) ® Adrenal cortex ® glucocorticoids, mineralocorticoids, androgens
Thyrotropin-releasing hormone (TRH) (+) ® thyroid-stimulating hormone (TSH) ®thyroid ® thyroxine, triiodothyronine
Gonadotropin-releasing hormone (GnRH) (+) ®(follicle-stimulating hormone {FSH}; luteinizing hormone {LH}) ® gonads ® estrogen, progesterone, testosterone
Dopamine (-) ® prolactin ® breast

adapted from Table 37-1: Fizgerald, P.A. and Klonoff, D.C. Hypothalamic and Pituitary Hormones, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p 604.

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Mechanisms of Hormone Action

Overview:hormone action mechanisms
- Hypothalamic/Pituitary hormones: all peptides;bind to target cell surface receptors


Human Growth hormone highlighted (left); Human Growth hormone binding protein highlighted (right); attribution James Madison University, Luke McGinty & Matt Ezzi (http://www.isat.jmu.edu/users/klevicca/isat454/RasMol_Round_Robin/Round_Robin_2001/454_midtermProject/HGHindex.htm)

GHRH, Somatostatin, PRH, TSH, CRH, ACTH, GnRH, FSH, LH, and Dopamine receptors:
- Seven-transmembrane-domain serpentine peptides
- Ligand binding ® conformational change (activating)
  - G protein coupling
    - G₁₄ protein :GnRH & TRH
    - G_i protein: dopamine receptor
    - G_s protein: other receptors noted above

GHRH, CRH, GnRH, TSH, ACTH, FSH, LH, and Dopamine receptors associated G protein-GTP complex® adenylyl cyclase activation ®cAMP production ® protein kinase activation ® intracellular protein phosphorylation ® hormonal effects

Dopamine receptor -- G_i protein coupling (lactotroph receptor system) ® ¯ decreased adenylyl cyclase activity ® ¯ decreased prolactin secretion

Growth hormone: a-GTP complex related to somatostatin receptors ®potassium channels ®inhibit growth hormone (GH) secretion

Thyrotropin-releasing hormone: G protein complexes related to thyrotrophs' TRH receptors ®phosphoinositide-specific phospholipase C ®cytoplasmic free calcium ®stimulating TSH secretion

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Growth hormone & Prolactin receptors:
- single peptides
- extracellular amino-terminal hormone-binding domains
- intracellular carboxyl terminal sequence activates JAK2 (tyrosine kinase) leading to intracellular protein tyrosine phosphorylation and gene regulation
- GH receptor fragments (GH binding protein, GHBP): bind 50% of circulating growth hormone

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