Mechanisms of Hormone Action

• Overview: hormone action mechanisms

  • Hypothalamic/Pituitary hormones: all peptides;bind to target cell surface receptors

• 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 and 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 and 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 and G protein complexes related to thyrotrophs' TRH receptors→phosphoinositide-specific phospholipase C→cytoplasmic free calcium→stimulating TSH secretion

• Growth hormone and Prolactin receptors

  • Single peptides

  • Extracellular amino-terminal hormone-binding domains

  • Intracellular carboxyl terminal sequence activates JAK2, which is a tyrosine kinase. 

    • Actiation of this tyrosine kinase leads to intracellular protein tyrosine phosphorylation and gene regulation.

  • GH receptor fragments (GH binding protein, GHBP) bind 50% of circulating growth hormone.

Reference: Fitzgerald, P.A. and Klonoff, D.C. Hypothalamic and Pituitary Hormones, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 603-618.

Reference: Biller, Beverly M. K. and Daniels, Gilbert, H. Neuroendocrine Regulation and Diseases of the Anterior Pituitary and Hypothalamus, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1972-1998