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Contraceptive Action of a Gonadotropin-Releasing Hormone II Analog in the Rhesus Monkey

Center for Investigation of Cell Regulation and Replication (T.M.S.-K.), San Antonio, Texas 78229; and The State Key Laboratory of Reproductive Biology (F.-Q.Y., P.W., S.-X.T., Y.-X.L.), Institute of Zoology, Beijing 100080, China

Address all correspondence and requests for reprints to: Theresa M. Siler-Khodr, Ph.D., Center for Investigation of Cell Regulation and Replication, 7711 Louis Pasteur, Suite 509, San Antonio, Texas 78229. E-mail: swgenetics{at}aol.com; or Yi-Xun Liu, Ph.D., The State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China. E-mail: liuyx{at}panda.ioz.ac.cn.

GnRH I (mammalian GnRH) was previously thought to be the only isoform of GnRH expressed in mammals, but GnRH II (chicken II GnRH) has now been identified in tissues of numerous mammalian species. Specific high-affinity receptors, which bind GnRH II and its analogs, have been identified throughout the reproductive tract, and GnRH II regulation of progesterone and human chorionic gonadotropin have been demonstrated. Thus, we hypothesized that GnRH II acts as a paracrine factor to regulate extrahypothalamic tissue functions and could be used as an effective contraceptive agent.

In these studies, we examined the effect of a stable analog of GnRH II (GnRH II analog) on ovarian steroidogenesis, implantation, and maintenance of pregnancy in the rhesus monkey. GnRH II analog or saline was administered by osmotic minipumps on d 1–6, d 6–11, or d 11–17 to cycling monkeys mated with fertile males. Circulating progesterone and estradiol were determined during the luteal phase, and the cycle length before, during, and after treatment was observed. Circulating monkey chorionic gonadotropin was used to determine implantation. In animals treated with GnRH II analog on d 1–6, no pregnancies resulted; but in saline-treated controls, five of eight animals (62.5%) became pregnant. In animals treated with analog on d 6–11, two of five (40.0%); and on d 11–17, one of three (33.3%); implanted and normal pregnancies ensued. Cycle length or progesterone production was not affected by analog treatment.

These data demonstrate that this GnRH II analog can act as a contraceptive agent when administered chronically around the time of ovulation or early luteal development. These findings suggest that GnRH II may play a role in reproductive physiology and that GnRH II analogs may serve as an effective, nonsteroidal, postcoital contraceptive.

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