The Effects of Perinatal Androgen Deprivation on Sexual Motivation in Male Rats

Abstract

Testosterone and its metabolites—estrogen and dihydrotestosterone— are involved in the brain sex differentiation during the perinatal period by binding to androgen receptors (AR) or estrogen receptors (ER). However, in the presence of flutamide (FLU), testosterone that is metabolized to estrogen will only bind to ER. Blockade of AR using FLU during the perinatal period could alter the levels of estrogen, which in turn, may modulate the sex differentiation of the brain. This study tested perinatal androgen deprivation on estrogen levels and in turn, its effects on sexual motivation paradigm in male rats.Animals (N=37) were divided into two groups: Group 1 received FLU (20 mg/kg; SC) during perinatal period (prenatal day 4 ‐ postnatal day 4) and Group 2 served as control. On postnatal day 65, these groups were divided into 3 subgroups (injected 5 days/week x 7 weeks): A. finasteride (20 mg/kg, SC), an α‐reductase inhibitor, B. letrozole (2 mg/kg, SC), an aromatase inhibitor and C. vehicle. Each male rat had a choice of approaching a cage containing a gonadally‐intact female or an ovariectomized (OVX) rat for 20 minutes. The movement of the male rat was video‐tracked by Any‐Maze. In addition, serum estrogen levels were measured using ELISA.Animals receiving FLU not only had high serum estrogen levels, but also exhibited no preference for the gonadally‐intact or the OVX female. On the other hand, the control‐vehicle group spent more time with the gonadally‐intact than the OVX rat. These results suggest that perinatal androgen deprivation in male rats results in high levels of estrogen and lack of sexual motivation towards gonadally‐intact female rats.