Antide-induced suppression of pituitary gonadotropin and ovarian steroid secretion in cynomolgus monkeys: premature luteolysis and prolonged inhibition of folliculogenesis following single treatment.
Administration of high-dose Antide to ovariectomized monkeys results in rapid, prolonged, and reversible inhibition of gonadotropin secretion. The present study examined whether similar long-term control would be manifested in the menstrual cycle of intact primates. Antide administration at a dose of either 3.0 or 18.0 mg/kg induced rapid suppression of bioassayable LH concentrations, precipitating a concurrent fall in serum progesterone concentrations from 7.9 +/- 3.6 and 5.8 +/- 1.0 ng/ml (mean +/- SEM) on the day of injection to 0.6 +/- 0.2 and 0.5 +/- 0.1 ng/ml by 2 days post-treatment, respectively. This Antide-induced luteolysis was accompanied by the premature onset of menses within 3 days. The next menses following Antide administration was delayed. Ultimately, folliculogenesis culminating in normal follicular-phase estradiol production, ovulation, and subsequent normal luteal-phase progesterone production did occur in all treated monkeys. Menses resumed 54 +/- 9 and 75 +/- 13 days after treatment with 3.0 and 18.0 mg/kg Antide, respectively. No allergic cutaneous or peripheral reactions were seen, even at the highest dose of Antide. Thus, the long duration of action of high-dose Antide reported earlier in ovariectomized monkeys is also demonstrated in intact primates. These findings, along with the apparent absence of histamine-release effects even at high doses, suggest that Antide is a GnRH antagonist deserving clinical evaluation.
Gordon
K
K
Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk 23510.
Williams
R F
RF
Danforth
D R
DR
Hodgen
G D
GD
D000818:Animals; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005498:Follicular Phase / Q000187:drug effects / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D008183:Luteal Phase / Q000187:drug effects / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism; D008252:Macaca fascicularis; D008597:Menstrual Cycle / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism
D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; C057022:iturelix