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Estrogen Suppresses Uterine Epithelial Apoptosis by Inducing Birc1 Expression

Division of Dermatology, Department of Medicine (Y.Y., W.-W.H., C.L., H.C., L.M.), Department of Molecular Biology and Pharmacology (L.M.), Washington University School of Medicine, St. Louis, Missouri 63110; Department of Cell and Molecular Biology (Y.Y.), Tulane University, New Orleans, Louisiana 70118; and Solange Gauthier Karsh Laboratory (A.M.), Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada K1H 8L1

Address all correspondence and requests for reprints to: Liang Ma, Division of Dermatology, Department of Medicine, Washington University, Campus Box 8123, 660 South Euclid Avenue, St. Louis, Missouri 63110. E-mail: lima{at}im.wustl.edu.

The decision whether or not a cell undergoes apoptosis is determined by the opposing forces of pro- and antiapoptotic effectors. Here we demonstrate genetically that estrogen can tip this balance toward cell survival in uterine epithelial cells by inducing the expression of baculoviral inhibitors of apoptosis repeat-containing 1 (Birc1), a family of antiapoptotic proteins. In neonatal mice, both 17β-estradiol and the potent synthetic estrogen diethylstilbestrol strongly suppress uterine epithelial apoptosis while markedly elevating Birc1 transcript level in an estrogen receptor--dependent manner. The induction of Birc1 before any effect on apoptosis suppression and failure of diethylstilbestrol to completely inhibit apoptosis in Birc1a-deficient uterine epithelium indicate a functional role for Birc1a in estrogen-mediated apoptosis suppression. In ovariectomized adult mice, expression of Birc1 is also induced by ovarian hormones, suggesting a role for these proteins in normal uterine physiology. We propose that by binding to active caspases, Birc1 proteins can eliminate them through proteasome degradation. These results for the first time establish Birc1 proteins as functional targets of estrogen in suppressing apoptosis in the uterus.

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα

Ligands:   17β-Estradiol  |  Diethylstilbestrol