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Endocrinology Vol. 141, No. 11 4056-4064
Copyright © 2000 by The Endocrine Society

ARTICLES

Differential Transcriptional Regulation of Rat Vasopressin Gene Expression by Estrogen Receptor {alpha} and ß1

Robert A. Shapiro1, Cong Xu1 and Daniel M. Dorsa1,2

Departments of Psychiatry and Behavioral Sciences
1 and Pharmacology
2 , University of Washington, Seattle, Washington 98195

Address all correspondence and requests for reprints to: Robert A. Shapiro, University of Washington, Psychiatry and Behavioral Sciences, Box 356560, Seattle, Washington 98195-6560. E-mail: shapiror{at}u.washington.edu

Neuronal expression of vasopressin messenger RNA (mRNA) and peptide has been shown to be estrogen dependent. A 5.5-kb genomic DNA fragment, 5' of the AVP coding region, was used in luciferase reporter assays to measure transcriptional activation by either estrogen receptor {alpha} or ß in response to various treatments. ER{alpha} and ERß displayed differential regulation of the AVP promoter. SK-N-SH cells transfected with ER{alpha} exhibited increased luciferase activity in response to estrogen, and the selective estrogen receptor modulators (SERMs), Tamoxifen, and ICI 182,780. Cells transfected with ERß exhibited a high constitutive activity, which is unchanged by exposure to SERMs but can be inhibited by estrogen. Deletion of 1.5 kb from the 5' end or mutation of a single estrogen response element (ERE)-like sequence resulted in loss of estrogen-dependent induction by ER{alpha} and increased the ability of estrogen to inhibit the high constitutive activity of ERß. The distal ERE-containing 1.5-kb fragment, when coupled to luciferase, is able to support both ER{alpha} and ERß mediated activation of transcription by estrogen. These results suggest that a single ERE in the distal 1.5-kb portion of the 5.5-kb fragment contains the primary positive estrogen responsive sequences for ER{alpha} and ERß. The data also suggest that sequences proximal to this element serve to inhibit transcription mediated by ERß.




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