Differential transcriptional regulation of rat vasopressin gene expression by estrogen receptor α and β

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 α or β in response to various treatments. ERα and ERβ displayed differential regulation of the AVP promoter. SK-N-SH cells transfected with ERα exhibited increased luciferase activity in response to estrogen, and the selective estrogen receptor modulators (SERMs), Tamoxifen, and ICI 182,780. Cells transfected with ERβ 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 ERα and increased the ability of estrogen to inhibit the high constitutive activity of ERβ. The distal ERE-containing 1.5-kb fragment, when coupled to luciferase, is able to support both ERα and ERβ 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 ERα and ERβ. The data also suggest that sequences proximal to this element serve to inhibit transcription mediated by ERβ.