Gene Expression Profiling of the Effects of Castration and Estrogen Treatment in the Rat Uterus1

The development and functions of female reproductive tis-sues are regulated by the actions of two major sex steroid hor-mones, estrogen and progesterone. To investigate estrogen-de-pendent gene expression in the rat uterus, we studied the effect of ovariectomy with or without estrogen treatment on the uter-ine expression of 3000 genes using cDNA microarrays. Many genes were regulated by either treatment, but only few were reciprocally regulated by these contrasting treatments. The pre-sent study confirms previous findings and identifies several genes with expressions not previously known to be influenced by estrogen. These genes include follistatin-related protein, Thy-1 glycoprotein, a-fodrin, CD24, immediate early response 5, in-sulin-like growth factor-binding protein 2, growth response pro-tein CL-6 (INSIG-1), ladinin1, class I major histocompatibility complex heavy chain, lactadherin, ezrin, and Fas-activated ser-ine/threonine kinase. Because of their function as regulators of proliferation and apoptosis, CD24, insulin-like growth factor-binding protein 2, and Fas/Fas ligand were examined further by immunohistochemical expression and tissue localization analy-sis. Our analysis confirms a contrasting regulation of these gene products by ovariectomy and estrogen treatment. The present 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. estradiol, gene regulation, mechanisms of hormone action, uteru