Transcriptional regulation of the mouse steroid 5α-reductase type II gene by progesterone in brain

The steroid 5α-reductase (5α-R) plays an important physiological role in the conversion of steroid hormones such as androgen and progesterone to their 5α-reduced derivatives. 5α-R type II (5α-R2), one of two 5α-R isoforms, is thought to be a key enzyme in the generation of neuroactive steroids in the brain, particularly allopregnanolone (AP), via the production of its precursor dihydroprogesterone from progesterone. In the present study, we investigated possible regulatory mechanisms of 5α-R2 gene expression by steroid hormones in the female mouse brain. We first cloned mouse 5α-R2 (m5α-R2) cDNA by degenerate PCR, and found that progesterone induced 5α-R2 gene expression to levels detectable by in situ hybridization in female mouse brains. Functional analysis of the m5α-R2 gene promoter by a transient expression assay with human progesterone receptor (PR) and androgen receptor (AR) expression vectors identified a progesterone and androgen regulatory element (m5α-R2 PRE/ARE). Results of an electrophoretic mobility shift assay revealed that both PR and AR homodimers bound directly to m5α-R2 PRE/ARE sequence. These findings suggest that the gene expression of m5α-R2 is transcriptionally regulated by progesterone in female brains.