Differential transcriptional regulation of rat vasopressin gene expression by estrogen receptor alpha and beta.

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 beta in response to various treatments. ER alpha and ER beta 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 ER beta 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 ER beta. The distal ERE-containing 1.5-kb fragment, when coupled to luciferase, is able to support both ER alpha and ER beta 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 ER beta. The data also suggest that sequences proximal to this element serve to inhibit transcription mediated by ER beta.