Evidence that gonadotropin-releasing hormone (GnRH) II stimulates luteinizing hormone and follicle-stimulating hormone secretion from monkey pituitary cultures by activating the GnRH I receptor

Mammalian gonadotropin-releasing hormone (GnRH) I is the neuropeptide that regulates reproduction. In recent years, a second isoform of GnRH, GnRH 11, and its highly selective type 11 GnRH receptor were cloned and identified in monkey brain, but its physiological function remains unknown. We sought to determine whether GnRH 11 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 11 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 11 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 11 as well as GnRH I. Furthermore, the combination of GnRH I and GnRH 11 was no more effective than either agonist alone. These results indicate that GnRH 11 stimulates FSH and LH secretion, but they also imply that this action occurs through the GnRH I receptor. The GnRH 11 receptors may have a unique function in the monkey brain and pituitary other than regulation of gonadotropin secretion.