A large number of sex differences in the central nervous system (CNS) of vertebrates have now been described. Such morphological dimorphisms may underlie well documented sex differences in behavior, in susceptibility to certain drugs, and in the incidence of some human mental disorders including autism, depression and schizophrenia. In many cases, neural sex differences have been shown to be due to gonadal steroid hormones acting early in development. However, the cellular and molecular mechanisms governed by hormones in the developing nervous system are not well understood. A simple neuromuscular system which is sexually dimorphic in many mammals has proven to be a valuable model system for identifying basic principals underlying the development of neural sex differences. Motoneurons of the spinal nucleus of the bulbocavernosus (SNB) of rats innervate striated perineal muscles involved in reproduction. The number of SNB motoneurons and the survival of SNB target muscles is extremely sensitive to androgen during perinatal development. It has recently been demonstrated that a putative neurotrophic molecule, ciliary neurotrophic factor (CNTF), can mimic some of the effects of early androgen in this system. Moreover, receptors to CNTF and to other neurotrophic molecules are present in the SNB system during the period of sexual differentiation. The effects of CNTF on the developing SNB system will be further characterized by identifying sites of production of CNTF and its receptors, and the in vivo site(s) of action of CNTF in this system. Cellular effects of CNTF and androgen will be contrasted to gain insight into the basis of the critical period for androgenic action. Finally, we will determined whether the expression of CNTF or other neurotrophic molecules is regulated by androgen, in order to evaluate the hypothesis that neurotrophic factors may mediate effects of gonadal steroids in the genesis of sexual dimorphism. The identification of such a mechanism would represent a breakthrough in our understanding of the development of neural sex differences. Because neurotrophic molecules implicated in the SNB system are expressed throughout the CNS of many vertebrates, including humans, information gained from work in this system will be relevant to understanding the development of less accessible dimorphic systems in the brain.
