RESPONSIVENESS OF THE CORPUS-LUTEUM OF THE RHESUS-MONKEY (MACACA-MULATTA) TO GONADOTROPIN IN-VITRO DURING SPONTANEOUS AND PROSTAGLANDIN F-2-ALPHA-INDUCED LUTEOLYSIS

The ability of luteal tissue from rhesus monkeys, collected from spont aneous and prostaglandin F-2 alpha (PGF(2 alpha)) induced luteolytic c ycles, to secrete progesterone in response to hCG or dibutyryl cAMP in vitro was assessed. It was expected that the corpus luteum exposed to PGF(2 alpha) would behave in a similar manner to the corpus luteum of normal cycles undergoing luteal regression. PGF(2 alpha) (10 ng mu l( -1) h(-1)) or vehicle (1 mu l h(-1)) was infused into the corpus luteu m from 7 days after the preovulatory oestradiol surge. Lutectomy was p erformed at 2, 3 and 4 days after the start of the intraluteal infusio n and at menses. Luteal progesterone content was determined and the se cretion of progesterone in response to hCG (10 miu ml(-1)) or dibutyry l cAMP (5 mmol l(-)) was evaluated in vitro. A third group of monkeys underwent lutectomy sequentially during the luteal phase and were grou ped by luteal age from days after the preovulatory oestradiol surge: e arly luteal (days 4-6), midluteal (days 7-9), late luteal (days 10-14) and menses. Immediately before luteal excision, an ovarian venous blo od sample was taken for progesterone determination. Approximately 2-5 mg of minced luteal tissue was incubated at 37 degrees C in 2 mi of Kr ebs-Ringer bicarbonate buffer for 2 h in the presence or absence of hC G or dibutyryl cAMP. In control and vehicle-infused monkeys, hCG cause d 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 pro gesterone 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(2 alpha) 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(2 alpha). This observation mimicked the even ts observed over the course of the normal or vehicle-infused luteal ph ase. The failure of hCG and dibutyryl cAMP to stimulate progesterone p roduction at menses implies that once luteolysis is complete, the inte grity of the steroidogenic response is unequivocally lost. The progres sive decline in responsiveness to hCG further suggests that receptor l oss is not a sudden event in the mechanism of PGF(2 alpha)-induced or spontaneous luteolysis, but a progressive process coincident with lute al ageing. These data strongly suggest that spontaneous and PGF(2 alph a)-provoked luteal regression are very similar with regard to progeste rone content, basal synthesis and sensitivity to gonadotrophin and fur ther support a physiological role for PGF(2 alpha) during luteolysis i n primates.