The results of our experiment clearly demonstrate that both isozymes of 5-R are expressed in prefrontal cortex of adult male rats. It was previously reported that 5-R type 2 is selectively expressed in the hypothalamus
(19, 23). Thus, T and DHT bind to a transcription factor, the androgen receptor, which in turn activates genes that carry out morphogenetic programs implicated in sexual differentiation processes in specific brain regions (1). The pattern of expression of 5-R type 2 presented in this study appears to be correlated with T levels, indicating that this isozyme may be positively modulated by androgen, as described previously during late fetal/ early post-natal life (1). Our results demonstrate for the first time that 5-R type 2 expression in the brain is regulated by DHT, a product of the encoded enzyme, via a form of feed-forward regulation. This regulatory mechanism is common among developmentally important genes
Our study demonstrated that 5-R type 1 expression is not controlled by androgen in the intact animal. However, it is negatively controlled by some testicular factors (in part by T and DHT) because there is a marked increase in 5-R type 1 expression in castrated animals, in which circulating T and DHT are low. Furthermore, T and DHT decrease the mRNA levels of 5-R type 1 in castrated animals. These findings are novel and surprising
Our data demonstrated an increase in 5-R type 1 expression in the castrated male rat that is hormonally similar to a female model.[b] This observation is consistent with a previous report that 5-R activity in liver, which expresses only 5-R type 1, is more active in female than in male rats /b.
. This finding suggests that both isozymes may play a role in the sexual dimorphism of the CNS, besides other functions. To our best knowledge, our study provides the first evidence that the expression of both 5-R isozymes in the brain, at least in the cerebral cortex, is regulated in opposite ways by androgens
This is why I think a lot of us get worse when we try and increase Testosterone and DHT. And why a lot of experience some improvement when take a 5ar inhibitor. Decreasing DHT increases 5ar1 expression in the CNS