Disparate Effects of Prostaglandins on Basal and Gonadotropin-Stimulated Progesterone Production by Luteal Cells Isolated from Rhesus Monkeys during the Menstrual Cycle and Pregnancy

Abstract

To examine the direct effects of prostaglandins (PG) on corpus luteum function in primates, luteal cells isolated from rhesus monkeys were incubated in the presence of PGE2 or PGF2α, either alone, or in combination with gonadotropin (hCG) or dibutyryl cyclic AMP. Luteal cells were obtained at Days 16–18 (4–7 days after the preovulatory LH surge; midluteal phase cells) and Days 21–22 (8–10 days after the LH surge; late luteal phase cells) of the menstrual cycle and at 160–166 days of gestation (term pregnancy cells). Under control conditions, luteal cells at these stages produced similar amounts of progesterone in vitro. Progesterone production by cells from midluteal phase of the menstrual cycle was significantly (P<0.05) increased in the presence of 50 ng PCE2/ml, with a maximal response at 5000 ng/ml. PGF2α was 10-fold less potent than PGE2 in stimulating progesterone production by midluteal phase cells. In contrast, the progesterone synthetic activity of luteal cells from late luteal phase of the cycle and at term pregnancy was unaltered by the presence of 5–5000 ng/ml of either PGE2 or PGF2α. PG (5000 ng/ml) stimulation of progesterone secretion by midluteal phase cells was less (P<0.01) than that elicited by the presence of 1000 ng hCG/ml and the combination of hCG and either PGE2 or PGF2α produced a response no different from that by hCG alone. Although cells from late luteal phase of the cycle and term pregnancy responded to 1000 ng hCG/ml with enhanced (P<0.01) progesterone production, the combination of hCG and 5000 ng/ml of either PGE2 or PGF2α failed to increase progesterone secretion. However, neither PG prevented the stimulation of luteal cell progesterone production by 1 mM dibutyryl cyclic AMP. Thus, PG mimicked gonadotropin stimulation of luteal cell steroidogenesis at midluteal phase of the menstrual cycle, but antagonized the stimulatory effect of hCG on luteal cells isolated later in the cycle and at term pregnancy. PG may act prior to the elevation of cellular cyclic AMP to block the mechanism of hCG stimulation of progesterone production by luteal cells. The data suggest that PG may have a potential luteotropic or luteolytic effect on luteal cells of the rhesus monkey, depending upon the "age" of the corpus luteum.