The aim of this study was to determine whether daily increasing doses of hCG could overcome luteal regression induced by PGF_2α in rhesus monkeys. Prostaglandin F_2α (10 ng μl⁻¹ h⁻¹) or vehicle (tham buffer; 1 μl h⁻¹) was infused directly into the corpus luteum for 7 days, beginning 7 days after the preovulatory oestradiol surge. hCG was injected i.m. in increasing doses (15, 30, 60, 90, 180, 360 and 720 iu) for 7 days, starting on the eighth day after the preovulatory oestradiol surge, or 1 day after the initiation of luteal infusion of PGF_2α or vehicle. Monkeys receiving vehicle plus hCG on the same days served as controls. Daily progesterone, oestradiol and hCG concentrations were determined from blood drawn from the saphenous or femoral vein, and the duration of the luteal phases were recorded. Where intraluteally infused PGF_2α resulted in premature, functional luteolysis, hCG always inhibited the luteolytic effect of PGF_2α; the secretory patterns of progesterone and oestradiol were augmented, and peak values were reached in concert with the highest concentration of hCG in the blood, and the luteal phase was significantly increased compared with those of untreated monkeys or with monkeys treated with PGF_2α alone or vehicle. Treatment with hCG alone or with PGF_2α vehicle also resulted in maintained luteal function and a significantly longer luteal phase, but both progesterone and oestradiol concentrations began to decline before hCG reached peak values in the circulation. Once the hCG regimen was concluded, luteal regression ensued and menses occurred at a time coincident with decreased steroid endometrial support. These results are the first to show that hCG can inhibit luteal regression induced by PGF_2α in vivo, and are contrary to results obtained in vitro using minced or sliced luteal cells, which indicates that PGF_2α inhibits the trophic action of LH or hCG on progesterone secretion. We conclude that in the rhesus monkey, hCG can completely abolish the luteolytic effect of PGF_2α through an unknown mechanism.

The ability of luteal tissue from rhesus monkeys, collected from spontaneous and prostaglandin F_2α (PGF_2α) induced luteolytic cycles, to secrete progesterone in response to hCG or dibutyryl cAMP in vitro was assessed. It was expected that the corpus luteum exposed to PGF_2α would behave in a similar manner to the corpus luteum of normal cycles undergoing luteal regression. PGF_2α (10 ng μl⁻¹ h⁻¹) or vehicle (1 μl h⁻¹) was infused into the corpus luteum from 7 days after the preovulatory oestradiol surge. Lutectomy was performed at 2, 3 and 4 days after the start of the intraluteal infusion and at menses. Luteal progesterone content was determined and the secretion of progesterone in response to hCG (10 miu ml⁻¹) or dibutyryl cAMP (5 mmol l⁻) was evaluated in vitro. A third group of monkeys underwent lutectomy sequentially during the luteal phase and were grouped by luteal age from days after the preovulatory oestradiol surge: early luteal (days 4–6), mid-luteal (days 7–9), late luteal (days 10–14) and menses. Immediately before luteal excision, an ovarian venous blood sample was taken for progesterone determination. Approximately 2–5 mg of minced luteal tissue was incubated at 37°C in 2 ml of Krebs–Ringer bicarbonate buffer for 2 h in the presence or absence of hCG or dibutyryl cAMP. In control and vehicle-infused monkeys, hCG caused an increase in luteal progesterone production during the mid-luteal and late luteal phases, but not at the early luteal phase or at menses; exposure to dibutyryl cAMP resulted in a significant increase in progesterone at all times except menses. The response of luteal tissue to hCG or dibutyryl cAMP progressively decreased as a function of luteal age. Luteal tissue treated with PGF_2α in vivo also exhibited a decreased response to progesterone production stimulated by hCG; that is, the response to hCG was inversely correlated with the duration of luteal infusion with PGF_2α. This observation mimicked the events observed over the course of the normal or vehicle-infused luteal phase. The failure of hCG and dibutyryl cAMP to stimulate progesterone production at menses implies that once luteolysis is complete, the integrity of the steroidogenic response is unequivocally lost. The progressive decline in responsiveness to hCG further suggests that receptor loss is not a sudden event in the mechanism of PGF_2α-induced or spontaneous luteolysis, but a progressive process coincident with luteal ageing. These data strongly suggest that spontaneous and PGF_2α-provoked luteal regression are very similar with regard to progesterone content, basal synthesis and sensitivity to gonadotrophin and further support a physiological role for PGF_2α during luteolysis in primates.