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Functional Differentiation of the Placental Syncytiotrophoblast: Effect of Estrogen on Chorionic Somatomammotropin Expression during Early Primate Pregnancy

Departments of Obstetrics, Gynecology, and Reproductive Sciences and Physiology (B.M., E.D.A.), Center for Studies in Reproduction, The University of Maryland School of Medicine, Baltimore, Maryland 21201; and Department of Physiological Sciences (G.J.P.), Eastern Virginia Medical School, Norfolk, Virginia 23501

Address all correspondence and requests for reprints to: Eugene D. Albrecht, Ph.D., Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Bressler Research Laboratories 11-019, 655 West Baltimore Street, Baltimore, Maryland 21201. E-mail: ealbrech{at}umaryland.edu.

Estrogen stimulates morphological and functional (i.e. steroidogenesis) differentiation of the primate placental trophoblast, and with advancing gestation there is an increase in estrogen and placental chorionic somatomammotropin (CS) mRNA and protein levels. To examine whether CS formation is regulated by estrogen, placental villous trophoblast CS was determined in baboons in which estradiol levels in uterine vein were increased 2- to 3-fold (P < 0.01) on d 60 of pregnancy (term = 184 d) by administration of aromatizable androstenedione on d 30–59 or estradiol benzoate on d 45–59 of gestation. Androstenedione and estradiol treatment resulted in a 75% decrease (P < 0.01) in placental whole villous CS-3 mRNA and CS protein levels, determined by Northern and Western blot analysis, on d 60, and a corresponding decrease in syncytiotrophoblast CS protein and maternal serum CS levels. In contrast, placental villous ⁵-3ß-hydroxysteroid dehydrogenase, 11ß-hydroxysteroid dehydrogenase-2, and P-450 aromatase protein levels were unaltered by androstenedione or estradiol treatment. Collectively, these results suggest that, in elevated levels, estrogen suppressed CS formation by villous syncytiotrophoblast during the first one third of primate pregnancy. Therefore, estrogen has very different and specific actions on steroid and peptide hormone biosynthesis within the placental trophoblast, which we propose are important in regulating placental function and promoting fetal-placental development in the primate.

This work was supported by NIH Research Grant R01 HD-13294.

Abbreviations: CS, Chorionic somatomammotropin; 11ß-HSD, 11ß-hydroxysteroid dehydrogenase; LDL, low-density lipoprotein; P-450scc, P-450 cholesterol side-chain cleavage; poly(A)⁺, polyadenylated (A)⁺; PRL, prolactin.