Steroid 5α-reductase isozymes in the adult female rat brain: central role of dihydrotestosterone

Abstract

The enzyme 5α-reductase (5α-R) (EC 1.3.99.5) exists as two isoforms, 5α-R type 1 (5α-R1) and 5α-R type 2 (5α-R2). 5α-R1 has been associated with catabolic functions whereas 5α-R2 has been associated with sexually dimorphic functions of the male. We recently demonstrated that both 5α-R isozymes are present in the central nervous system (CNS) of the adult male rat and are regulated in an opposing way by androgens. This finding raises the question as to whether both isozymes play a role in the sexual dimorphism of the CNS, besides other functions. To test this hypothesis, it is essential to study the regulation of both isozymes by androgens in the female. In this work, we studied the effects of testosterone (T) and dihydrotestosterone (DHT) on mRNA levels of both 5α-R isoforms in the prefrontal cortex of the adult female rat by one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis. Our results demonstrate for the first time that 5α-R2 mRNA is slightly regulated by T and DHT in females. Surprisingly, 5α-R1 mRNA is not regulated by T in the intact female, whereas it is very positively regulated by DHT, a more potent androgen than T. These data indicate the great sexual dimorphism in the CNS with respect to both 5α-R isozymes, and suggest a crucial role of DHT in the sexual dimorphism of the CNS in the female. These results open up a new research line that may lead to a better understanding of the physiology of the CNS.