Chorionic gonadotropin (CG) produced by fetal tissues extends the functional lifespan of the primate corpus luteum during early pregnancy; endogenous CG or administration of human CG (hCG) enhances progesterone and relaxin production by the primate corpus luteum. The current study was designed to compare the ability of recombinant (r) and urinary (u) hCG to stimulate luteal function and to assess the role of progesterone in the regulation of luteal relaxin secretion during simulated early pregnancy (SEP) by concomitant administration of hCG and the 3b-hydroxysteroid dehydrogenase inhibitor trilostane. Rhesus monkeys received injections of either r-hCG or u-hCG in increasing doses (15-2880 mIU/dose BID) for 9 days beginning on day 9 of the luteal phase to simulate the rising serum CG of early pregnancy. An additional group received r-hCG with trilostane (500 mg/dose BID) to reduce luteal progesterone production. Daily serum samples were assayed for hCG, progesterone, and relaxin. hCG levels were not different between the r-hCG and u-hCG treatment groups during or following treatment. Serum hCG concentrations peaked 1 day after the final injection in monkeys receiving r-hCG (2759 q 120 mIU/ml) and u-hCG (2120 q 60 mIU/ml) and dropped below 5 ng/ml by 10 days after the final treatment in both groups. Progesterone rose rapidly after initiation of hCG treatment and peaked in r-hCG (14.4 q 2.8 ng/ml) and u-hCG (11.9 q 1.4 ng/ml) treated monkeys 4 days after initial administration. Relaxin levels peaked in monkeys treated with r-hCG (400 q 148 pg/ml) and u-hCG (323 q 85 pg/ml) within 4 days of the final hCG treatment. Trilostane + r-hCG treatment reduced progesterone concentrations to <1 ng/ml (p<0.01 vs. r-hCG alone) within 1 day of initial treatment and maintained low levels for the entire treatment interval. Trilostane did not alter luteal relaxin production (377 q 76 pg/ml) when compared with monkeys receiving r-hCG only. Thus, r-hCG and u-hCG were equally efficacious in stimulating the steroidogenic and peptidergic activities of the monkey corpus luteum during SEP. Progesterone deprivation during r-hCG administration did not alter circulating relaxin levels, suggesting that progesterone is not a major regulator of relaxin production by the primate corpus luteum during early pregnancy.
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