IDENTIFICATION OF A FUNCTIONAL ANDROGEN RESPONSE ELEMENT IN THE PROMOTER OF THE GENE FOR THE ANDROGEN-REGULATED ALDOSE REDUCTASE-LIKE PROTEIN-SPECIFIC TO THE MOUSE VAS-DEFERENS

Mouse vas deferens protein (MVDP), a member of the aldo-keto reductase superfamily, is exclusively produced in the epithelial cells of the d eferent duct under androgenic regulation. To better understand androge n-regulated MVDP gene expression, the location and sequences of androg en response elements (AREs) in the 5'-flanking DNA were determined. Se quence analysis revealed two putative AREs as follows: one between pos itions -1186 and -1171 (distal ARE) and the other between -111 and -97 (proximal ARE). To study hormonal regulation, fragments of the MVDP p romoter region, extending from residue -1804 to +41, were linked to th e chloramphenicol acetyltransferase (CAT) reporter gene and cotransfec ted with a human androgen receptor expression vector into T47D cells i n a transient expression assay. A minimal region (-121 to +41) was ide ntified as being sufficient for androgen-regulated gene expression. A mutation in proximal ARE almost completely abolished androgen inductio n of CAT. One copy of the sequence TGAAGT tcc TGTTCT, cloned in the op posite orientation in front of the thymidine kinase promoter, confers androgen responsiveness to the CAT reporter gene. Androgen transcripti onal activity was not detected with the distal ARE. The data provide s trong evidence that transcriptional regulation of the MVDP gene occurs via the sequence TGAAGT tcc TGTTCT.