An integrated program of human and animal research is proposed. It will examine neural and social factors underlying influences of androgens and estrogens on development, particularly of the cerebral cortex and cognition. Human research will include studies of two groups exposed prenatally to unusual hormone milieus: 1. children with congenital adrenal hyperplasia (CAH) in which the adrenal gland overproduces androgen; and 2. females with Turner's Syndrome (TS) in which the ovary fails to produce hormones. Study 1 will investigate the hypothesis that changes in toy preferences of girls with CAH reflect social factors, such as parental perceptions and treatment, rather than or in addition to hormonal influences on the developing brain. Children with CAH will be videotaped alone, and with both parents, playing with sex-typed and neutral toys. Paper and pencil measures will also be used to measure gender identification and sex-typed parental perceptions, and to obtain broad measures of behavior. Study 2 will examine cognition in TS patients using several tests, some measuring functions associated with males (e.g., visuospatial ability and language lateralization), some measuring functions associated with females (e.g., verbal fluency and perceptual speed) and some unrelated to gender. These will distinguish among 3 hypotheses concerning cognitive development in TS females: 1. impaired masculine neural systems; 2. impaired masculine and feminine systems; or 3. general impairment, unrelated to sexual differentiation. Toy preferences of girls with TS will be studied to determine if changes in play behavior parallel adult cognitive function. Research on rats will investigate mechanisms underlying hormonal influences on the developing cerebral cortex and provide information for interpreting clinical studies. Data suggest that hormonal influences on cortical development differ from those established elsewhere. We will use standard techniques of hormone removal and administration to examine this. We will also examine the distribution of cortical estrogen receptors to delineate possible sites of hormone action and to test the hypothesis that sex difference in cortical development result from sex differences in receptor distribution. This research will provide information as to how hormonal and social factors act singly and in combination to influence cortical and cognitive development. It will provide information regarding the relevance to human development of animal models and will increase understanding of the behavioral consequences of prenatal exposure to sex-typed hormones.
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