The promoter of the rat 5alpha-reductase type 1 gene is bidirectional and Sp1-dependent

In many androgen target tissues, testosterone is reduced to the more potent androgen, dihydrotestosterone, by steroid 5alpha-reductase. Two isoforms of 5alpha-reductase, type 1 and type 2, have been cloned. They are differentially expressed and regulated. To determine the mechanisms of regulation of 5alpha-reductase type 1 expression, we have cloned its 5'upstream region and defined its promoter. The proximal 5'upstream region of 5alpha-reductase type 1 displays all the features of a CpG island and has numerous Sp1 binding sites. By transient transfection assays, we have identified a bidirectional promoter activity in this region; this activity was highest in the negative orientation, in the direction of the methyltransferase Nsun2 (predicted) gene. Promoter activity, in either orientation, was lost in Sp1 deficient cells but was rescued following co-transfection with a Sp1 expression vector. Thus, the 5'upstream region of rat 5alpha-reductase type 1 contains a bidirectional promoter with an activity that is Sp1-dependent.