The Androgen Receptor Is Selectively Involved in Organization of Sexually Dimorphic Social Behaviors in Mice

It is well established that sexually dimorphic neural regions are organized by steroid hormones during development. In many species, neonatal males are exposed to more testosterone than their female littermates, and ultimately it is the estradiol, produced by aromatization of testosterone, that affects sexual differentiation. However, the androgen receptor also plays an important role in the masculinization of brain and behavior. Here we tested the hypothesis that sexually dimorphic social and odor preference behaviors can be differentiated by a nonaromatizable androgen during development by treating female mice on the day of birth (PN0) with dihydrotestosterone (DHT). Control mice received a single vehicle injection on PN0. Adults were gonadectomized, treated with estradiol, and tested for social behaviors. In contrast with control females, females treated on PN0 with DHT, like male controls, exhibited a preference for female-soiled vs. male-soiled bedding, a preference to investigate a female vs. a male and reduced c-Fos-immunoreactivity (ir) in several neural areas after exposure to male-soiled bedding. However, females treated with DHT on PN0 had normal female-typical sexual behavior. The number of calbindin-ir cells in the preoptic area is sexually dimorphic (males more than females), but females given DHT on PN0 had intermediate numbers of calbindin-ir neurons, not significantly different from control males or females. Our data demonstrate that organization of social and olfactory preferences in mice can be affected by perinatal DHT and lends support to the role of androgen receptor in organization of sexual differentiation of brain and behaviors.