Transcriptional regulation of the mouse steroid 5alpha-reductase type II gene by progesterone in brain.
The steroid 5alpha-reductase (5alpha-R) plays an important physiological role in the conversion of steroid hormones such as androgen and progesterone to their 5alpha-reduced derivatives. 5alpha-R type II (5alpha-R2), one of two 5alpha-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 5alpha-R2 gene expression by steroid hormones in the female mouse brain. We first cloned mouse 5alpha-R2 (m5alpha-R2) cDNA by degenerate PCR, and found that progesterone induced 5alpha-R2 gene expression to levels detectable by in situ hybridization in female mouse brains. Functional analysis of the m5alpha-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 (m5alpha-R2 PRE/ARE). Results of an electrophoretic mobility shift assay revealed that both PR and AR homodimers bound directly to m5alpha-R2 PRE/ARE sequence. These findings suggest that the gene expression of m5alpha-R2 is transcriptionally regulated by progesterone in female brains.
Matsui
Daisuke
D
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan.
Sakari
Matomo
M
Sato
Takashi
T
Murayama
Akiko
A
Takada
Ichiro
I
Kim
Misun
M
Takeyama
Ken-ichi
K
Kato
Shigeaki
S
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis / Q000235:genetics*; D024506:5' Flanking Region; D000595:Amino Acid Sequence; D000728:Androgens / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003001:Cloning, Molecular; D018387:Codon, Initiator; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D011374:Progesterone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020218:Response Elements; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation
D000728:Androgens; D018387:Codon, Initiator; D012333:RNA, Messenger; D011374:Progesterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase