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BOR - Papers in Press, published online ahead of print June 11, 2003.
Biol Reprod 2003, 10.1095/biolreprod.103.015420
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Submitted January 19, 2003
Returned for revision February 3, 2003
Accepted May 14, 2003

Mechanisms of Hormone Action


Gene Expression Profiling of the Effects of Castration and Estrogen Treatment in the Rat Uterus

XuXia Wu , See-Tong Pang , Lena Sahlin , Agneta Blanck , Gunnar Norstedt , and Amilcar Flores-Morales *

* To whom correspondence should be addressed. E-mail: amilcar.flores{at}molmed.ki.se.

Abstract

The development and functions of female reproductive tissues are regulated by the actions of two major sex steroid hormones, estrogen and progesterone. To investigate estrogen dependent gene expression in the rat uterus, we studied the effect of ovariectomy with or without estrogen treatment on uterine expression of 3000 genes using cDNA microarrays. While many genes were regulated by either treatment, only few were reciprocally regulated by these contrasting treatments. Our study confirms previous findings and identifies several genes whose expressions have not previously been known to be influenced by estrogen. These genes include follistatin-related protein, Thy-1 glycoprotein, {alpha}-fodrin, CD24, immediate early response 5, insulin-like growth factor binding protein 2, growth response protein CL-6 (INSIG-1), ladinin1, class I MHC heavy chain, lactadherin, ezrin and Fas-activated serine/ threonine kinase. Due to their function as regulators of proliferation and apoptosis, CD24, insulin-like growth factor binding protein 2 and Fas/Fas-L were examined further the by immunohistochemical expression and tissue localization analysis. Our analysis confirms a contrasting regulation of these gene products by ovariectomy and estrogen treatment. This study identifies novel mediators of estrogen actions in the uterus and provides genome-wide expression data from which novel hypotheses regarding uterine function can be generated.



Key words: Mechanisms of Hormone Action • Estradiol • Gene regulation • Uterus


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