MECHANISMS OF HORMONAL CONTROL OF NEURAL DEVELOPMENT

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There is a marked morphological sex difference in the brain of the rat: the sexually dimorphic nucleus of the preoptic area (SDN-POA), which is several-fold larger in male than in female rats. Neurons in this region bind high levels of steroids during development, and the size of the nucleus appears to be determined by the hormonal environment at this time. Because the sex difference in the SDN-POA is so dramatic, and because it can be manipulated by hormonal treatments during development, it provides an opportunity to study the basic mechanisms underlying brain development and its sexual differentiation. The aim of the proposed research is to investigate the possibility that the SND-POA is part of an interrelated sexually dimorphic neural system, and that components of this system exert trophic influences on one another during development. Specifically, three groups of studies will be conducted. The first group will use procedures similar to those used in previous studies of the SDN-POA, to identify and quantify sex differences in other steroid-binding regions of the brain, and to describe the time course for the development of these sex differences. The second group of studies will use anterograde an retrograde tract-tracing techniques to identify possible projections between the SDN-POA and other neural regions that bind steroids. The third group of studies will use lesions and steroid implants to investigate the possibility that these projections are necessary for differentiation of the SDN-POA, and that one mechanism involved in sexual differentiation of the brain is a steroid-related, transsynaptic potentiation of neuronal survival. These studies will help elucidate the mechanisms involved in development of a specific neural sex difference, the SDN-POA. In addition, the information gained should prove relevant to our understanding of mechanisms underlying neural organization and development in general. This understanding could aid in prevention or amelioration of neurological disorders. The proposed research may also provide information related to the developmental consequences of hormone exposure during pregnancy.