Dose-related actions of GnRH II analog in the cycling rhesus monkey.

Introduction: Gonadotropin-releasing hormone (GnRH) II expression, specific high-affinity receptors for GnRH II and its potent bioactivity in human and baboon tissues led us to hypothesize that GnRH II is a bioactive peptide in primates. We recently demonstrated the contraceptive activity of GnRH II analog in rhesus monkeys. In the present experiment, we extended those studies to the dose-related action of this analog on parameters of luteal function and conception.

Methods: GnRH II analog (0-32 microg/day) or saline was administered via osmotic minipumps for 6 days (Days 1-6 postovulation) to regularly cycling rhesus monkeys mated with fertile males around the time of ovulation. Cycle dynamics was monitored through circulating luteinizing hormone, progesterone and estradiol. Pregnancy was determined by circulating chorionic gonadotropin concentrations.

Results: Progesterone production (Days 3-11) was significantly less (p<.05) for animals treated with 2, 4 or 8 microg/mL GnRH II analog than for controls, yet with higher doses of GnRH II analog (i.e., 16 or 32 microg/day), luteal progesterone was not different from that of saline-treated controls. The length of the luteal phase in all treated groups was similar to that of controls. In 18 animals mated at the time of ovulation and then treated with GnRH II analog (2-32 microg/day), no pregnancies resulted. In saline-treated controls, five of eight animals (62.5%) became pregnant. Thus, the contraceptive activity of this GnRH II analog did not correlate with luteal progesterone inhibition.

Conclusions: These data demonstrate a dose-related action of GnRH II analog on luteal progesterone and establish the contraceptive activity of 2-32 microg/day GnRH II analog administered postovulation.