Suppression of human chorionic gonadotropin by progestational steroids

The dynamics of the secretion of human chorionic gonadotropin (hCG) were studied by culturing explants of normal term placentas for as long as 144 hours. A significant accumulation of immunoreactive hCG (beta-subunit) was first detected at 48 to 72 hours, and a sixfold increase in hCG was observed in control culture medium at 144 hours. Compared to control cultures, progesterone (P < 0.001) in physiologic tissue levels of 5 to 20 micrograms/ml, pregnenolone (P < 0.001), 20 micrograms/ml, and 20 alpha-dihydroprogesterone (P < 0.001), 20 micrograms/ml, suppressed the secretion of hCG throughout the study period. Progesterone decreased the secretion of hCG in a dose-response manner (r = -0.8S87, P < 0.1). No suppression of hCG was observed in the presence of cortisol, testosterone, dihydrotestosterone, 17 beta-estradiol, or estriol. The secretion of human chorionic somatomammotropin was unchanged in the presence of progesterone. The augmented hCG response in the presence of dibutyl cAMP (P < 0.001) was significantly, but not completely, suppressed by progesterone 20 micrograms/ml culture medium (P < 0.01). Under these conditions progestational steroids or their immediate metabolites suppress the secretion of hCG, and they may be responsible for the decline in the levels of hCG during pregnancy.