Estrogen receptor (ER) β, a modulator of ERα in the uterus

Zhang Weihua, Shigehira Saji, Sirpa Mäkinen, Guojun Cheng, Elwood V. Jensen, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticle

440 Scopus citations

Abstract

Many of the effects of estrogens on the uterus are mediated by ERα, the predominant ER in the mature organ. Because of the poor reproductive capacity of ERβ knockout (BERKO) female mice (small litter size, multiple-resorbed fetuses), the role of uterine ERβ was explored. In the immature uterus, ERα and ERβ are expressed at comparable levels in the epithelium and stroma, and 17β-estradiol (E2) treatment decreases ERβ in the stroma. The immature uterus of untreated BERKO mice exhibits elevated levels of progesterone receptor (PR) and the proliferation-associated protein, Ki-67. It also exhibits exaggerated responsiveness to E2, as indicated by enlargement of the lumen, increase in volume and protein content of uterine secretion, induction of the luminal epithelial secretory protein, complement C3, and its regulatory cytokine IL-1β, and induction of vascular endothelial growth factor and insulin-like growth factor 1 but not its receptor. As expected, E2 increased PR in the stroma and decreased it in the luminal epithelium of wild-type mice. In the BERKO uterus, E2 induced PR in the stroma but did not down-regulate it in the epithelium. Increased cell proliferation and exaggerated response to E2 in BERKO suggest that ERβ plays a role in modulation of the effects of ERα and in addition (or as a consequence of this) has an antiproliferative function in the immature uterus.

Original languageEnglish (US)
Pages (from-to)5936-5941
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number11
DOIs
StatePublished - May 23 2000

ASJC Scopus subject areas

  • General

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