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Differential regulation of steroid 5-reductase isozymes expression by androgens in the adult rat brain

J. M. TORRES^* and E. ORTEGA^*,,1

^* Department of Biochemistry and Molecular Biology, Faculty of Medicine, and
Institute of Neurosciences, University of Granada, 18012 Granada, Spain

¹Correspondence: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada, Spain. E-mail: esortega{at}ugr.es

The enzyme 5-reductase (5-R) is present in many mammalian tissues, including the brain. The physiological importance of 5-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 5-reduced derivatives, precursors of allopregnanolone and tetrahydroDOC, potent allosteric modulators of the -aminobutyric acid receptor (GABA_A-R). 5-R occurs as two isoforms, 5-R type 1 (5-R1) and 5-R type 2 (5-R2). We studied the effects of T and DHT on the mRNA levels of both 5-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 5-R are expressed in the cerebral cortex of adult rats. The gene expression of 5-R type 2 is under the positive control of T and DHT. The gene that codes for 5-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 5-R isozymes in the physiology of the central nervous system.—Torres, J. M., Ortega, E. Differential regulation of steroid 5-reductase isozymes expression by androgens in the adult rat brain.

Key Words: transcriptional regulation • prefrontal cortex

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