5alpha-reductase 2 inhibition impairs brain defeminization of male rats: reproductive aspects.
The present study was carried out to determine whether 5alpha-reductase 2 (5alpha-R2) metabolic pathway plays a key role in brain sexual differentiation. The inhibition of 5alpha-R2 by finasteride (20 mg/kg/day) from gestational day 19 to postnatal day 5 has long-term effects on sexual behavior and reproductive physiology detected only in adult life. Sexual maturation assessed by timing of preputial separation was unchanged. Finasteride-treated males were able to mate with untreated females which became pregnant but exhibited increased rate of pre-implantation loss. The subfertility observed was probably due to abnormally shaped sperm, since the sperm number was not altered. While plasma testosterone was enhanced, LH levels were not changed. The copulatory potential was not affected and all finasteride-treated rats presented male sexual behavior. Despite this, 53% of them showed homosexual behavior when pretreated with estradiol, suggesting an incomplete brain defeminization. These results indicate that 5alpha-R2 acts in brain sexual differentiation of male rats. Moreover, we suggest that 5alpha-R2 not only produces essential metabolites that act together with estradiol in brain sexual differentiation but also protects the brain from the damaging effects of estradiol excess.
Ribeiro
Camilla Moreira
CM
Department of Pharmacology, Institute of Biosciences, Sao Paulo State University- UNESP, 18618-000 Botucatu, SP, Brazil.
Pereira
Oduvaldo Câmara Marques
OC
D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018120:Finasteride / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction; D012726:Sexual Behavior, Animal; D012741:Sexual Maturation; D013076:Sperm Count; D013739:Testosterone / Q000097:blood
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D013739:Testosterone; D018120:Finasteride; D007986:Luteinizing Hormone