Selective placental secretion of estrogens into fetal and maternal circulations.

Abstract

Estradiol levels in the fetal rhesus monkey are extremely low as compared to fetal estrone or maternal estrone or estradiol concentrations. At least two mechanisms are possible: 1) the fetus rapidly metabolizes estradiol, 2) the placenta selectively secretes estradiol primarily into the maternal circulation. To test these hypotheses we infused rhesus fetuses with [3H]estradiol and simultaneously infused their mothers with [14C]estradiol. From steady-state [3H]- and [14C]estradiol concentrations in fetal and maternal circulations we were able to determine that the primary mechanism responsible for the low fetal estradiol levels is a selective placental secretion of estradiol toward the maternal circulation. The estimated maternal estradiol secretion rate was 124 μg/day, whereas the estimated fetal estradiol secretion rate was approximately 0 μg/day. The fetal estradiol production rate of 4.5 μg/day was accounted for by conversion of strone to estradiol in the fetus and transfer of estradiol from mother to fetus. Very little estradiol, however, was transferred across the placenta between the fetal and maternal circulations. Only 0.8 μg/day was transferred from fetus to mother and 1.4 μg/day from mother to fetus. The metabolic clearance rate of the fetus (125 liters/day) was approximately equal to that of the mother (186 liters/day). We also conducted similar experiments using radiolabeled estrone. In contrast to the selective placental secretion observed found that estrone was secreted into both maternal and fetal circulations in substantial quantities. The estimated fetal estrone secretion rate was 64 μg/ day and that of the mother was 22 μg/day. The production rate of estrone in the mother of 57 μg/day was approximately equal to that of the fetus of 64 μg/day because significant quantities of maternal estrone were derived from conversion of maternal estradiol to aternal estrone. In contrast, maternal estradiol was derived almost entirely from direct placental secretjon. We conclude: 1) The low levels of estradiol in the fetal circulation can be explained predominantly by a selective placental secretion of estradiol into the maternal circulation. The placenta secretes very little or no estradiol directly into the fetal circulation. 2) Estrone is secreted in substantial quantities into both fetal and maternal circulations. 3) Maternal stradiol and fetal estrone are derived mainly from direct placental secretion, whereas fetal estradiol is derived primarily from conversion of estrone to estradiol in the fetus. Maternal estrone, on the other hand, originates from two primary sources: direct placental secretion and conversion of estradiol to estrone in the mother. 4) The placenta is relatively impermeable to transplacental passage of both estrone and estradiol.