HORMONAL REGULATION OF BRAIN AND BEHAVIOR DEVELOPMENT

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This project is designed to investigate the role of steroid hormones, estrogen in particular, in the development of brain and behavior. Currently, two models of sexual differentiation of brain and behavior are thought to exist. In mammals, estrogen, derived from testicular androgens, is thought to cause masculine development of neuroanatomy and sexual behaviors. in birds, estrogen that is secreted directly by the female ovary is thought to cause feminine development of copulatory behaviors. Unlike this more typical pattern of avian sexual differentiation, the neural song control system of zebra finches (which is much larger in males that sing than in females that do not) is thought to follow the mammalian pattern and masculinize under the influence of estradiol derived from androgen secreted by the testes in males. The main data in support of that theory are that treatment of females with estrogen in the first few weeks after hatching will cause masculine development of their neural song systems and allow them to sing in adulthood. However, a variety of experiments are incompatible with the idea that estrogen derived from testicular secretions is normally the substance that promotes masculine development in males. At present, it is unclear how the song system normally sexually differentiates. This proposal is designed to test two hypotheses: (i) the zebra finch song system is similar to the copulatory system of birds in that it is masculinized not by the presence of steroids derived form the testes but by the absence of estradiol and/or other ovarian factors, and (ii) the song system of zebra finches is similar to the copulatory system of mammals in that masculinization occurs under the influence of estradiol, either directly or indirectly. The experiments are designed to test how ovarian and testicular tissue, separately and in concert, influence sexual differentiation of the song and copulatory systems in zebra finches. Further. the studies will investigate the potential roles of estrogen and nerve growth factor receptors in the development of brain and behavior. Embryonic zebra finches will be treated with an inhibitor of estrogen synthesis or estrogen to determine the effects on the song and copulatory systems of (i) such alterations in estrogen levels, and (ii) testicular tissue in genetic females (which the estrogen synthesis inhibitor induces) and ovarian tissue in genetic males (which estradiol induces). Then, estrogen receptors will be assayed throughout the brain at a variety of developmental stages. Finally, sex differences in nerve growth factor binding will be investigated throughout development, and the effect on that binding of manipulating estrogen levels during the period of sexual differentiation will be studied.