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Evidence that Gonadotropin-Releasing Hormone (GnRH) II Stimulates Luteinizing Hormone and Follicle-Stimulating Hormone Secretion from Monkey Pituitary Cultures by Activating the GnRH I Receptor¹

Division of Endocrinology and Metabolism³ James Graham Brown Cancer Center,⁴ University of Louisville, Louisville, Kentucky 40202

Mammalian gonadotropin-releasing hormone (GnRH) I is the neuropeptide that regulates reproduction. In recent years, a second isoform of GnRH, GnRH II, and its highly selective type II GnRH receptor were cloned and identified in monkey brain, but its physiological function remains unknown. We sought to determine whether GnRH II stimulates LH and FSH secretion by activating specific receptors in primary pituitary cultures from male monkeys. Dispersed pituitary cells were maintained in steroid-depleted media and stimulated with GnRH I and/or GnRH II for 6 h. Cells were also treated with Antide (Bachem, King of Prussia, PA), a GnRH I antagonist, to block gonadotropin secretion. In monkey as well as rat pituitary cultures, GnRH II was a less effective stimulator of LH and FSH secretion than was GnRH I. In both cell preparations, Antide completely blocked LH and FSH release provoked by GnRH II as well as GnRH I. Furthermore, the combination of GnRH I and GnRH II was no more effective than either agonist alone. These results indicate that GnRH II stimulates FSH and LH secretion, but they also imply that this action occurs through the GnRH I receptor. The GnRH II receptors may have a unique function in the monkey brain and pituitary other than regulation of gonadotropin secretion.

¹ Supported by NIH grants HD 19546, CA 60871 (to S.S.K.), the Walter F. and Avis Jacobs Foundation, and the Commonwealth of Kentucky Research Challenge Fund. Y.O. is an International Research Fellow from Tokyo Medical and Dental University (Tokyo, Japan).

² Correspondence: Stephen J. Winters, Division of Endocrinology and Metabolism, University of Louisville Health Sciences Center, ACB-A3G11, 530 S. Jackson Street, Louisville, KY 40202. FAX: 502 852 4978; sjwint01{at}louisville.edu

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