Gonadotropin versus steroid regulation of the corpus luteum of the rhesus monkey during simulated early pregnancy

During the nonconceptive cycle in primates, progesterone is a likely intermediary for several LH-dependent events in the ovary including ovulation, luteinization of the follicle wall, and maintenance of the developed corpus luteum. To determine whether progesterone is an important local factor in the ability of chorionic gonadotropin (CG) to enhance luteal structure and function in early pregnancy, rhesus monkeys received hCG in a dose-escalating regimen (15-2880 IU twice daily) beginning on Day 9 of the luteal phase of the natural menstrual cycle to simulate the rapid rise in serum CG levels associated with early pregnancy. Some animals were concomitantly treated with the 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) inhibitor trilostane (500 mg twice daily) to suppress progesterone production during gonadotropin stimulation. Corpora lutea were removed after 1, 3, 6, and 9 days of treatment (n = 3-4 per group); time-matched control tissues were obtained from untreated animals (n = 3 per group). Treatment with hCG prevented both the decrease in luteal wet weight (p < 0.05) and the histologic indices of luteal regression seen in controls during the menstrual cycle. However, coadministration of the progesterone synthesis inhibitor led to early declines in luteal wet weight (p < 0.05) and luteal cell size compared to treatment with hCG alone. Luteal progesterone receptor (PR) mRNA content increased (p < 0.05), but the percentage of cells staining positive for immunoreactive PR declined (p < 0.05) over the treatment interval in all groups. CG administration alone and in combination with trilostane increased PR staining intensity in some luteal cells within 1 day of treatment; intensely staining cells persisted around vascular elements after 9 days of treatment with hCG+trilostane but not with hCG alone. These data suggest that some, but not all, actions of CG to maintain the primate corpus luteum in early pregnancy are mediated by progesterone via a receptor-mediated pathway.