Luteal production of steroids and prostaglandins during simulated early pregnancy in the primate: Differential regulation of steroid production by chorionic gonadotropin

Abstract

Stimulation of the primate corpus luteum (CL) by endogenous chorionic gonadotropin (CG) in early pregnancy, or by exogenous human (h)CG in simulated early pregnancy, results in a transient elevation of serum progesterone (P) and a persistent elevation of serum 17β-estradiol (E). Luteal prostaglandins (PD) may play a role in these responses. The objective of the current study was to correlate luteal PG production and steroidogenic response of CL in vitro with patterns of serum steroids during simulated early pregnancy. CL were removed from rhesus monkeys (n = 26) at 0 h, 9 h, 3 days, 6 days, and 10 days, during prolonged CG exposure of simulated early pregnancy. Dispersed cells were incubated in vitro at 37°C for 8 h. Changes in basal production of P were not significantly correlated with patterns of serum steroids. Maximal stimulation of P production by hCG in vitro (stimulated minus basal) continuously declined (p < 0.01) from 0 h (x̄ ± SE, 59.6 ± 17.9 ng/ml) to 10 days (4.7 ± 1.8 ng/ml) of simulated early pregnancy. In contrast to patterns of response to hCG, the level of enhancement in P production in response to a maximally stimulatory dose of dibutyryl (db) cyclic adenosine 3',5'-monophosphate (cAMP) declined (p < 0.05) from 0 h (52.4 ± 17.6 ng/ml) to 3 days (20.3 ± 8.4 ng/ml), but was maintained through 10 days (23.7 ± 11.6 ng/ml) of simulated early pregnancy. As such, desensitization to gonadotropin, which occurred in terms of P production, appears to involve an event subsequent to stimulation of adenylate cyclase. The continued decline in luteal production of P in response to hCG, but not dbcAMP, through Day 10 of simulated early pregnancy, suggests that there are different temporal patterns for gonadotropin and cAMP desensitization. Several disparities existed between luteal production of P and that of E throughout simulated early pregnancy. Basal E production in vitro increased after 3 days of simulated early pregnancy (p < 0.05). Maximal stimulation of E production by hCG in vitro (stimulated minus basal) tended to increase between 0 h (12.8 ± 6.8 pg/ml) and 3 days (128.8 ± 54.4 pg/ml) and was maintained through 6 days (120.7 63.3 pg/ml) of simulated early pregnancy (p = 0.1). A maximally stimulatory dose of dbcAMP elicited patterns of E that were similar to those induced by hCG. Thus, the dichotomy between luteal E and P production during simulated early pregnancy is manifested in vitro as divergent patterns of basal production and differential responses to the same stimuli. As such, these data support the notion that production of E and P by the CL are differentially regulated during early pregnancy in primates. Similar to basal P production, changes in basal production of prostaglandin (PG) E2, PGF(2α), and 6-keto-PGF(1α) by CL were not significantly correlated with patterns of serum steroids. However, production of PGE2 tended to increase during the period that serum P fell (p = 0.08). The negative correlation between luteal production of PGE2 and patterns of serum P may indicate that further study of these relationships is warranted.