Proposal Number: 94-21431 Principal Investigator: Lustig, Robert H. The brain consists of billions of neurons which must interconnect to form specific cell groups and fiber tracts. The gonadal hormones, estrogen and androgens, have profound effects on specific cell groups in the brain. It is believed that the gonadal steroid environment during brain development dictates the organization of the brain and results in sex differences in brain organization. Participating in these sex differences may be the influence of the androgens and estrogens on the development of neural contacts through the nerve cell axons and dendrites. However, studies of these connections in the intact developing brain are difficult at best. Therefore, Dr. Lustig has elegantly proposed to address the question of gonadal steroid modulation of axon and dendrite development using in vitro cell lines endogenously expressing receptors for the steroid hormones, or genetically altered to express androgen or estrogen receptors. The proposed studies will investigate the effects of androgens and estrogens on axon outgrowth and arborization, on dendritic spine and gap junction formation in vitro, and assess the molecular events involved in cellular morphology and connectivity. These studies will provide new information on the manner by which estrogen and androgen elicit the cell biological events necessary for appropriate interneuronal connectivity during development. Such studies may serve as a basis for beginning to define the etiology and ontogeny of brain sexual dimorphisms, and the role of sex hormones in the development of cognition and behavior.
