The relationship of estrogen to placental steroidogenesis in the baboon

In previous studies in pregnant baboons, estrogen deprivation produced by the administration of the estrogen antagonist MER-25 resulted in a decline in plasma progesterone. In the present study, pregnant baboons in whom the corpus luteum-bearing ovary was removed early in pregnancy were used to distinguish between a luteal or placental effect of this estrogen deprivation. MER-25, administered from days 35 through 48 of pregnancy, resulted in a significant decline in plasma progesterone, indicating a direct placental action of estrogen deprivation on progesterone production. In a second experiment using intact pregnant baboons, concomitant administration of the nonsteroidal estrogen diethylstilbestrol (DES) prevented the inhibitory effect of MER-25 on placental progesterone, indicating that the effect was due to antiestrogenic action of MER-25 and not to some other pharmacological effect of the antagonist. Since DES administration alone had no effect on plasma progesterone levels, the role of estrogen may be a permissive action. The administration of MER-25 did not inhibit estradiol production in intact pregnant baboons with or without corpora lutea. When DES was administered to intact pregnant baboons, alone or together with MER-25, there was a significant decrease in plasma estradiol concentrations, which was only reversed after the cessation of treatment. These studies indicate that estrogen, perhaps by different mechanisms, may be important in the regulation of placental estradiol and progesterone production in the primate.