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.
ASJC Scopus subject areas