Androgenic mechanisms of sexual differentiation of the nervous system and behavior

Testicular androgens are the major endocrine factor promoting masculine phenotypes in vertebrates, but androgen signaling is complex and operates via multiple signaling pathways and sites of action. Recently, selective androgen receptor mutants have been engineered to study androgenic mechanisms of sexual differentiation of the nervous system and behavior. The focus of these studies has been to evaluate androgenic mechanisms within the nervous system by manipulating androgen receptor conditionally in neural tissues. Here we review both the effects of neural loss of AR function as well as the effects of neural overexpression of AR in relation to global AR mutants. Although some studies have conformed to our expectations, others have proved challenging to assumptions underlying the dominant hypotheses. Notably, these studies have called into question both the primacy of direct, neural mechanisms and also the linearity of the relationship between androgenic dose and sexual differentiation of brain and behavior.