Rapid inhibitory effects of an LHRH agonist implant on the oestrogen-induced LH surge and the induction of a defective luteal phase after an agonist-induced ovulation in the macaque
Three experiments were performed to evaluate in detail pituitary-ovarian function during the first 21 days after treatment with a lutelnizing hormone releasing hormone (LHRH) agonist implant. First, six adult macaques with normal menstrual cycles received an LHRH agonist implant during the late luteal or early follicular phase. To investigate the rapidity of effects on pituitary responsiveness the macaques were treated with 50 g LHRH at the time of implant (day 0) and at days 4, 10 and 21. Effects on serum LH and FSH were determined on basal samples and at 30 and 60 mm. At 4 days, LH and FSH were elevated as a result of the Implant and no further response to LHRH challenge was observed. By 10 days, LH had returned to the pretreat ment range but was unresponsive to the LHRH challenge; by 21 days, LH was lower than the pretreatment range and again L1{RH failed to induce a significant response. Serum FSH concentrations also declined during treatment, but in contrast to LH, a significant response to LHRH was observed on day 10. Secondly, the ability to respond to an oestrogen provocation test was examined in six macaques with normal menstrual cycles treated with the LIIRH agonist implant during the late luteal or early follicular phase and 7 days later wIth 50 pg/kg oestradlol benzoate in oil s.c. to induce an LH/FSH surge. In control animals, oestrogen treatment resulted in a positive feedback surge, reaching a maximum at 48 h post-injection. In contrast, agonist-treated animals showed complete abolition of the expected increase in UI and FSH. Thirdly, the ability of late follicular phase implanta tion of LHRH agonist to induce a mid-cycle-like LHJFSH surge was studied by treating four macaques with LHRH agonist implant on days 9/10 of the follicular phase. An LHJFSII surge occurred the next day and was followed by an elevation in serum progesterone concentrations which reached normal luteal phase values in two macaques but were below normal in the remaining two animals. All four macaques demonstrated a premature decline in serum pro gesterone by day 10 of the luteal phase. These results show that LHRH agonist implant causes rapid desensitization of the pituitary gonadotroph. When treatment is commenced during the late luteal or early follicular phase, the ability of oestrogen to induce an LH/FSII surge is abolished as early as day 7, showing that a direct oestrogen-induced component is not expressed in the desensitized pituitary. If the agonist implant is delayed until the late follicular phase, the resulting LH/FSH surge appears to induce ovulation although the subsequent luteal phase is shortened, presumably by the absence of LH pulses and declining basal LH concentrations.