Stimulation of primate luteal function by recombinant human chorionic gonadotropin and modulation of steroid, but not relaxin, production by an inhibitor of 3 beta-hydroxysteroid dehydrogenase during simulated early pregnancy.

Abstract

CG produced by fetal tissues extends the functional lifespan of the primate corpus luteum during early pregnancy. Previous studies showed that urinary hCG administered to monkeys to simulate the rising CG levels associated with early pregnancy enhanced both progesterone (P) and relaxin (RLX) production by the corpus luteum. The current study was designed: 1) to compare the ability of recombinant (r) and urinary (u) hCG to stimulate luteal function, and 2) to assess the role of P in the regulation of luteal RLX secretion during simulated early pregnancy by concomitant administration of hCG and the 3 beta-hydroxysteroid dehydrogenase inhibitor trilostane to reduce P production. Rhesus monkeys received injections of either r-hCG or u-hCG (Ares Serono) in increasing doses (15-2880 IU/dose, twice daily) for 9 days beginning on day 9 of the luteal phase (n = 5/group). An additional group (n = 4) received r-hCG as described above, with concomitant oral administration of trilostane (500 mg/dose twice daily; Sanofi Winthrop). Daily serum samples were assayed for hCG by immunoradiometric assay, steroid hormones by RIA, and RLX by enzyme-linked immunosorbent assay. Serum hCG levels typically were not different between the r-HCG and u-hCG groups during or after treatment. Concentrations of hCG peaked 1 day after the final injection in monkeys receiving r-hCG (mean +/- SEM. 2759 +/- 120 mIU/mL) and u-hCG (2120 +/- 60 mIU/mL) and dropped below 5 mIU/mL by 10 days after the final treatment in all groups. Both r-hCG and u-hCG stimulated luteal P and RLX production. Progesterone levels rose rapidly after the initiation of hCG treatment and peaked in animals receiving r-hCG (14.4 +/- 2.8 ng/mL) and u-hCG (11.9 +/- 1.4 ng/mL) 4 days after initial administration. RLX levels peaked in the r-hCG (400 +/- pg/mL) and u-hCG (323 +/- 85 pg/mL) groups within 4 days of the final hCG treatment. Trilostane with r-hCG reduced P concentrations to very low levels (< 0.5 ng/mL; P < 0.01) within 1 day of administration compared to those in animals receiving r-hCG only and maintained these low levels for the entire treatment interval. Nevertheless, trilostane administration did not alter luteal RLX production, with serum levels peaking at 377 +/- 76 pg/mL. These data indicate that r-hCG and u-hCG were equally efficacious in stimulating the steroidogenic and peptidergic activities of the corpus luteum during simulated early pregnancy. In addition, P deprivation during r-hCG administration did not alter circulating RLX levels, suggesting that P is not a major regulator of RLX production by the primate corpus luteum during early pregnancy.