Differential regulation of steroid 5alpha-reductase isozymes expression by androgens in the adult rat brain.
The enzyme 5alpha-reductase (5alpha-R) is present in many mammalian tissues, including the brain. The physiological importance of 5alpha-R in the brain derives from its capability to convert testosterone (T) to a more potent androgen, dihydrotestosterone (DHT), and to convert progesterone and deoxycorticosterone (DOC) to their respective 5alpha-reduced derivatives, precursors of allopregnanolone and tetrahydroDOC, potent allosteric modulators of the gamma-aminobutyric acid receptor (GABA(A)-R). 5alpha-R occurs as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2). We studied the effects of T and DHT on the mRNA levels of both 5alpha-R isozymes in the prefrontal cortex of the adult rat, using an accurate and precise method that combines the high specificity of one-step quantitative RT-PCR with the sensitivity of capillary electrophoresis. Our results demonstrate that both isozymes of 5alpha-R are expressed in the cerebral cortex of adult rats. The gene expression of 5alpha-R type 2 is under the positive control of T and DHT. The gene that codes for 5alpha-R type 1 is not constitutive, because its expression is negatively regulated by T and DHT. These results open up a new research line that may lead to a better understanding of the role of 5alpha-R isozymes in the physiology of the central nervous system.
Torres
J M
JM
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada, Spain.
Ortega
E
E
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D013196:Dihydrotestosterone / Q000097:blood / Q000494:pharmacology*; D019075:Electrophoresis, Capillary; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
D007527:Isoenzymes; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase