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Endocrinology Vol. 144, No. 2 701-710
Copyright © 2003 by The Endocrine Society

ARTICLE

Global Transcription Profiling of Estrogen Activity: Estrogen Receptor {alpha} Regulates Gene Expression in the Kidney

Scott A. Jelinsky, Heather A. Harris, Eugene L. Brown, Kathryn Flanagan, Xiaochun Zhang, Christopher Tunkey, KehDih Lai, Malcolm V. Lane, Donna K. Simcoe and Mark J. Evans

Genomics Department (S.A.J., E.L.B., K.F., C.T.), Wyeth Research, Cambridge, Massachusetts 02140; and Women’s Health Research Institute (H.A.H., X.Z., K.L., M.V.L., D.K.S., M.J.E.), Wyeth Research, Collegeville, Pennsylvania 19426

Address all correspondence and requests for reprints to: Dr. Mark Evans, Wyeth Research, 500 Arcola Road, Collegeville, Pennsylvania 19426. E-mail: evansm{at}wyeth.com.

Estrogen receptors (ERs) are expressed in numerous organs, although only a few organs are considered classical targets for estrogens. We have completed a systematic survey of estrogen regulation of approximately 10,000 genes in 13 tissues from wild-type and ERßKO mice treated sc with vehicle or 17ß-estradiol (E2) for 6 wk. The uterus and pituitary had the greatest number of genes regulated by E2, whereas the kidney had the third largest number of regulated genes. In situ hybridizations localized E2 regulation in the kidney to the juxtamedullary region of the cortex in both the mouse and rat. The ED50 for gene inductions in the kidney was 3 µg/kg·d, comparable with the 2.4 µg/kg·d ED50 for c-fos induction in the uterus. E2 regulations in the kidney were intact in ERßKO mice, and the ER{alpha}-selective agonist propylpyrazole triol acted similarly to E2, together suggesting an ER{alpha}-mediated mechanism. Several genes were induced within 2 h of E2 treatment, suggesting a direct activity of ER{alpha} within the kidney. Finally, the combination of the activation function (AF)1-selective agonist tamoxifen plus ER{alpha}KOCH mice expressing an AF1-deleted version of ER{alpha} allowed delineation of genes with differing requirements for AF1 or AF2 activity in the kidney.




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