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

Department of Molecular Medicine,³ Karolinska Institutet, 171 76 Stockholm, Sweden Division for Reproductive Endocrinology,⁴ Department of Woman and Child Health, Karolinska Institutet, 171 76 Stockholm, Sweden Section for Obstetrics and Gynecology,⁵ Department of Clinical Science, Huddinge University Hospital, 171 76 Stockholm, Sweden Division of Urology,⁶ Department of Surgery, Chang Gung Memorial Hospital, Tao Yuan 333, Taiwan

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 the uterine 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 present 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, -fodrin, CD24, immediate early response 5, insulin-like growth factor-binding protein 2, growth response protein CL-6 (INSIG-1), ladinin1, class I major histocompatibility complex heavy chain, lactadherin, ezrin, and Fas-activated serine/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 analysis. 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.

¹ Supported by the Swedish Research Council (grants 3972 and 14782), the Swedish Society for Medical Research, the Swedish Cancer Society (grant 1996-800-07XBB), AstraZeneca, and Karolinska Institute. A.F.-M. is partially supported by the University of Applied Sciences (UDCA), Bogota, Colombia. S.T.P. is supported by the Chang Gung Memorial Hospital, Taiwan.

² Correspondence: Amilcar Flores-Morales, Department of Molecular Medicine, Karolinska Hospital Building L8:01, 171 76 Stockholm, Sweden. FAX: 468 51776180; amilcar.flores{at}molmed.ki.se

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