Dose-related actions of GnRH II analog in the cycling rhesus monkey.
BACKGROUND
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.
Siler-Khodr
Theresa M
TM
Center for Investigation of Cell Regulation and Replication, San Antonio, TX 78229, USA. cicrr4@aol.com
Yu
Fu-Qing
FQ
Wei
Peng
P
Tao
Shi-Xin
SX
Coulhart
Susan
S
Mactyszczyk
Shari
S
Lui
Yi-Xun
YX
D000818:Animals; D003271:Contraceptive Agents, Female; D003338:Corpus Luteum / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D005306:Fertilization / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007986:Luteinizing Hormone / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D010060:Ovulation; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis / Q000097:blood
D003271:Contraceptive Agents, Female; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; C047717:LHRH, His(5)-Trp(7)-Tyr(8)-