Estrogen inhibition of basal and gonadotropin-stimulated progesterone production by rhesus monkey luteal cells in vitro

To assess the direct effect of estrogen on primate luteal function, including the ability of estrogen to counteract a gonadotropic stimulus, luteal cells isolated from corpora lutea of rhesus monkeys were incubated in vitro in the presence of estrogen, human chorionic gonadotropin (hCG), or estrogen and hCG combined. Luteal cells were obtained during the mid-luteal (day 15–19 of the menstrual cycle; 5–8 days after the preovulatory LH surge) and late luteal (day 21–25 of the cycle; 9–12 days after the LH surge) phase of the menstrual cycle. Under basal conditions (no exogenous hormones), progesterone production by mid-luteal phase cells was significantly (P < 0.01) greater than that by late luteal phase cells and significantly (P < 0.01) decreased by the addition of 1000 and 10,000 ng 17β-estradiol (E₂)/ml. Ten-fold less E₂ (100 ng/ml) significantly (P = 0.01) reduced basal progesterone production by late luteal phase cells, but not by mid-luteal phase cells. E2 and estrone inhibited luteal cell progesterone production in a similar fashion, with 1000 ng/ml of either estrogen causing a 50% reduction in progesterone synthesis. In contrast, estriol was at least 50-fold less active than E₂. Progesterone production by mid-luteal phase cells was enhanced (both P < 0.01) by the addition of 1 and 100 ng hCG/ml alone. However, in the presence of 100 ng E₂/ml, a level of 1 ng hCG/ml failed to increase progesterone production and the stimulatory effect of 100 ng hCG/ml was significantly (P < 0.05) diminished. Late luteal phase cells failed to respond to low (1 ng/ml) levels of hCG with enhanced progesterone production despite the absence of exogenous estrogen. The data provide in vitro evidence of the ability of estrogen to inhibit the gonadotropin-sensitive progesterone synthetic activity of primate luteal cells. These findings support a physiological role for estrogen in the regulation of the functional capacity of the primate corpus luteum during its lifespan in the non-fertile menstrual cycle.