2000 WHRG Grant Program

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Dynamics of Estrogen Receptor Alpha and Beta Expression in Rat UterusJenny M. Jones, Ph.D.
School of Medicine, University of Maryland, Baltimore

The steroid hormone estrogen plays a vital role in the development and function of the female and male reproductive systems. Estrogen's effects are mediated by two specific estrogen receptors (ERs), ER± and the more recently discovered ER². ER² is currently thought to modulate cellular responses to estrogen by acting as a transdominant repressor of ER±. This has significant implications for understanding the mechanism of action of estrogen and estrogen-like compounds and their impact on women's health and disease. Estrogen levels increase during both the estrous cycle and pregnancy. Preliminary data from this laboratory has shown that estrogen inhibits ER² mRNA expression in the rat uterus, leading us to hypothesize that (1) uterine ER² expression will vary during the estrous cycle and pregnancy, and (2)ER± and ER² may be differentially expressed in uterine luminal epithelium, glandular epithelium, stroma, vascular endothelium, and myometrium. Our four specific aims are to define the temporal and spatial dynamics of ER± and ER² gene expression in the rat uterus during the estrous cycle and throughout pregnancy: (1) As an in vivo model to evaluate estrogen-dependent ER expression in the uterus, we will initially determine the temporal changes in ER± and ER² mRNA levels in ovariectomized rats following administration of estrogen in a range of concentrations; (2) In subsequent studies we will measure uterine ER± and ER² mRNA expression at various time points in normal cycling female rats and in gravid female rats throughout pregnancy. Specific ER mRNAs will be detected by RT-PCR; (3) Using in situ hybridization we will extend these experiments to localize ER± and ER² mRNA specific uterine cell types, including luminal and glandular epithelium, stroma, endometrium, and myometrium; (4) Finally, using immunohistochemical methods, we will identify the location of ER± and ER² protein in these uterine tissue compartments for comparison with sites of mRNA expression.

These studies have a strong likelihood of succeeding because preliminary studies have shown that ER± and ER² can be detected in rat uterine tissue, the hypotheses follow logically from the preliminary data, and the specific aims are achievable using proven, well-established protocols. The results should make an important contribution to the existing knowledge in the area of estrogen regulation of reproductive processes, and should lay the foundation for further avenues of research in this important field.