Nursing Pharmacology Chapter 32: Hypothalamic and Pituitary Hormones
Hypothalamic/Pituitary hormones: all peptides;bind to target cell surface receptors
Seven-transmembrane-domain serpentine peptides
Ligand binding: conformational change (activating)
G14 protein :GnRH and TRH
Gi protein: dopamine receptor
Gs 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 Gi 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
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