Suppression of luteal function by a luteinizing hormone-releasing hormone antagonist during the early luteal phase in the stumptailed macaque monkey and the effects of subsequent administration of human chorionic gonadotropin

Abstract

In previous studies a single sc injection of the LHRH antagonist [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10 ]LHRH during the luteal phase of the stumptailed macaque menstrual cycle caused a transient suppression of serum LH and progesterone concentrations. To investigate whether a more prolonged suppression of LH release during the early luteal phase could result in a sustained suppression of progesterone, 10 monkeys were treated with 3 consecutive daily injections of 300 micrograms LHRH antagonist/kg beginning on days 0 (n = 2), 1 (n = 1), 2 (n = 1), 3 (n = 2), 4 (n = 2), and 5 (n = 2) after the LH surge. When the antagonist was administered on the day of the LH surge, serum concentrations of bioactive LH were still elevated on the following day, but then fell to low levels. Serum progesterone concentrations were subnormal in these monkeys for the next 10 days, but recovered toward the late luteal phase. In the 8 monkeys receiving antagonist starting between days 1-5 after the LH surge, serum concentrations of bioactive LH were suppressed to near the detection limit of the assay for 4 days after the first injection. Seven of the 8 monkeys demonstrated a progressive decline in serum progesterone concentrations to undetectable values which remained for the duration of the luteal phase. In the remaining monkey the decline in progesterone was less marked; this animal presented a normal progesterone profile 3 days after the last antagonist injection. Premature menses occurred in all 8 monkeys; the next ovulation occurred 18.9 +/- 0.3 days after the last antagonist injection. To test luteal function after antagonist treatment during the early luteal phase and to mimic the rescue of the corpus luteum during a fertile cycle and assess the contraceptive effects of antagonist, hCG in daily doses of 30, 60, 90, 180, and 360 IU was administered starting on day 7 of the luteal phase to monkeys previously treated with three daily injections of 300 micrograms antagonist/kg during the early luteal phase. Control monkeys received hCG injections alone. In the controls, hCG administration elevated serum progesterone concentrations to 15-20 ng/ml. In three monkeys in which antagonist administration did not commence until day 5 or 6, hCG overcame the suppressive effect of the antagonist. However, in seven monkeys in which antagonist administration began on days 1-4, hCG caused only a small progesterone rise (maximal range, 1.8-4.9 ng/ml), about 20% of that observed in control monkeys receiving hCG.(ABSTRACT TRUNCATED AT 400 WORDS)