The sexual differentiation of the mammalian brain is of basic importance to reproductive biology and developmental neuroscience. Since the discovery of structural sex differences in the brain and their modification by the gonadal hormonal environment perinatally, it has been assumed that structural sex differences underlie one or more of the functional sex differences. This laboratory has focused on two of the structural sex differences in the rat brain, the Sexually Dimorphic Nucleus of the Preoptic Area (SDN) and the Anteroventral Periventricular Nucleus (AVPV), the SDN because it is one of the most marked sex differences and the AVPV because it responds to gonadal hormones in a direction opposite to that exhibited by the SDN. Recent evidence, however, suggests that the AVPV differentiates much later, perhaps due to the activity of postpubertal gonads. One study (Specific Aim IV) is proposed to determine when the AVPV does become sexually dimorphic and if postpubertal hormonal activity is responsible for its differentiation. The other aims relate to the SDN, its function, developmental hormonal sensitivity and the question whether growth factors mediate steroid action on its differentiation. A unique animal preparation has been developed - an animal with a unilaterally masculinized SDN. Although thus far documented only in the genetic male, it is likely that we can produce a genetic female with one SDN feminine and the other masculinized. First, we will determine the reproductive physiological and behavioral potential of these unique animals through classical techniques of reproductive neuroendocrinology and then include these animals in electrical stimulation and in some cases, lesion studies to elucidate the possible function(s) of the SDN with particular emphasis on prolactin (Specific Aim I). Although the rat with the unilaterally masculinized SDN offers a unique model for functional studies, the nucleus still has to be further characterized (Specific Aim II). Since it is possible that there may be two critical periods for the masculinization of the SDN, we plan to study the SDN and the reproductive function of animals subjected to hormonal manipulations prenatally and late-postnatally (Specific Aim III). Finally, we plan using the unilaterally modified SDN as a model, to determine whether specific growth factors play a role in masculinization of the brain (Specific Aim V). Recently, the concept of sexual differentiation has been extended to the structure of the human brain and even to gender orientation. It is only by a clear understanding of this process in laboratory animals that sound conclusions can be made about our own species.
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