Nucleic Acids Research, 2002, Vol. 30, No. 6 1387-1393
© 2002 Oxford University Press
Transcriptional regulation of the mouse steroid 5
-reductase type II gene by progesterone in brain
1Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan and 2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
The steroid 5
-reductase (5-R) plays an important physiological role in the conversion of steroid hormones such as androgen and progesterone to their 5-reduced derivatives. 5-R type II (5-R2), one of two 5-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 5-R2 gene expression by steroid hormones in the female mouse brain. We first cloned mouse 5-R2 (m5-R2) cDNA by degenerate PCR, and found that progesterone induced 5-R2 gene expression to levels detectable by in situ hybridization in female mouse brains. Functional analysis of the m5-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 (m5-R2 PRE/ARE). Results of an electrophoretic mobility shift assay revealed that both PR and AR homodimers bound directly to m5-R2 PRE/ARE sequence. These findings suggest that the gene expression of m5-R2 is transcriptionally regulated by progesterone in female brains.
* To whom correspondence should be addressed at: Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0022, Japan. Tel: +81 3 5841 8478; Fax: +81 3 5841 8477; Email: uskato{at}mail.ecc.u-tokyo.ac.jp
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