Sex differences in brain and behavior are a result of the perinatal hormonal environment. Exposure to testicular androgens during critical developmental periods can permanently alter the anatomy, biochemistry, and physiology of the central nervous system. A major question is how do the gonadal steroid hormones regulate the differentiation of the brain at the cellular level. It is likely that the hormones act through fundamental developmental mechanisms, such as controlling how many cells are born, how such cells migrate to reach their targeted destinations, and whether or not they survive. In this Small Grant for Exploratory Research, Dr. Tobet will exploit recent technological advances to examine the mechanisms by which gonadal steroid hormones influence neuron migration during brain development. He has identified a molecule in radial glial, a particular cell type of the brain, that could play a role in hormone-dependent cell migration. Dr. Tobet will now localize this molecule in the brains of developing males and females and then determining whether its synthesis is regulated by gonadal steroid hormones. In addition, he will establish an in vitro culture system to examine cell movements and contacts directly and under defined and manipulatable conditions. The results from this work will provide new insights leading towards understanding the biochemical steps involved in the actions of steroid hormones on the developing nervous system. The identification and characterization of molecules that regulate the translation of gonadal steroid signals into permanent changes in brain structure and ultimately function are essential for determining the process of sexual differentiation. The importance of these hormonal effects is underscored by evidence of sex differences and androgen influences in the susceptibility to certain syndromes, learning disabilities, and neurological disorders.
