Journal of Clinical Endocrinology & Metabolism, Vol 65, 1020-1025, Copyright © 1987 by Endocrine Society

ARTICLES

Adenosine 3',5'-monophosphate, prostaglandins, and epinephrine stimulate the secretion of immunoreactive gonadotropin-releasing hormone from cultured human placental cells

F Petraglia, AT Lim and W Vale
Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037.

Cell culture and biochemical procedures were used to identify and study the possible mechanisms regulating the secretion of GnRH-like immunoreactivity (GnRH-LI) from human placenta. Monolayer primary cultures of trophoblasts were established after mechanical and enzymatic dispersion of normal human term placenta. The cultured cells stained immunocytochemically positive with anti-GnRH serum, and GnRH-LI extracted from the cells eluted from high performance liquid chromatography with the same retention time as authentic GnRH. One week after plating, exposure to high concentrations of K+ or to various doses of veratridine, a Na+ ionophore, increased GnRH-LI release into the culture medium. This effect was reversed by Ca2+ antagonists (cobalt, EGTA, and verapamil). Dibutyrylcyclic AMP, forskolin, theophylline, and theobromine also increased GnRH-LI concentrations in the medium of cultured placental cells in a dose-related manner, as did prostaglandins E2 and F2 alpha and epinephrine. The effect of epinephrine on GnRH-LI concentrations was mimicked by isoproterenol and reversed by propranolol, suggesting an effect mediated by beta- adrenergic receptors. These results indicate that GnRH-LI release from cultured human placental cells is stimulated by the opening of ionic channels and activation of the adenylate cyclase/cAMP system, and that prostaglandins and epinephrine may be involved in the regulation of GnRH-LI release from human placenta.

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