Regulation of functional differentiation of the placental villous syncytiotrophoblast by estrogen during primate pregnancy.

By using the baboon as an in vivo model for the study of the endocrinology of human pregnancy, studies in the authors' laboratories have shown that the primate placenta is an estrogen target tissue and that estrogen, via interaction with the estrogen receptor, regulates functional differentiation of the syncytiotrophoblast, which is manifest as an upregulation of key components of the progesterone biosynthetic pathway and the metabolism of corticosteroids critical to placental-fetal development. Thus, estrogen exerts specific stimulatory effects on the receptor-mediated uptake of low density lipoprotein by, and expression of, the P-450 cholesterol side-chain cleavage enzyme within the syncytiotrophoblast, thereby promoting the production of progesterone. Concomitantly, there is an estrogen-dependent developmental regulation of the 11beta-hydroxysteroid dehydrogenase enzyme system in the syncytiotrophoblast, which enhances transplacental oxidation of maternal cortisol to cortisone and leads to maturation of the fetal hypothalamic pituitary adrenocortical axis late in gestation. Consequently, estrogen has a central, integrative role in modulating the dialogue and signaling system operating between the placenta and fetus that results in the maintenance of pregnancy and the development of adrenocortical self-sufficiency that are essential for maturation of the fetus and neonatal survival after birth.