Effects of testosterone on brain mRNA levels of steroid 5α-reductase isozymes in early postnatal life of rat

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), and both are present in the brain. 5α-R1 has been proposed as a constitutive enzyme that essentially plays a catabolic and neuron protective role whereas 5α-R2 has been associated with sexually dimorphic functions of the male. In this work, we studied the effects of testosterone (T), the masculinizing hormone of the central nervous system (CNS), on mRNA levels of both 5α-R isoforms in the prefrontal cortex of male and female rats during the postnatal sexual differentiation of the CNS in the rat, using one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis (LIF-CE). We found an increase in 5α-R2 mRNA levels in both male and female rats after T treatment, while 5α-R1 mRNA levels were decreased in the same experimental conditions. Our results clearly indicated that T regulates the expression of both 5α-R1 and 5α-R2 genes in an opposite manner and independently of the sex. This could point to a crucial role of T in the sexual dimorphism for both 5α-R isozymes in the neonatal brain. These results open up a new research line that could improve understanding of the role of 5α-R isozymes in the physiology of the CNS.