This is a proposal for the continuation of a Research Scientist Development Award, now termed an Independent Scientist Award (KO2). During the first term of this award 60 experimental and control monkeys were created that had either normal or atypical prenatal exposure to androgen. Androgen exposures were of 40 days or less duration and critically timed to the start of the second or third trimester of pregnancy. Prenatal androgen exposure was reduced by twice daily administration of flutamide, an androgen receptor blocker. Weekly injections of testosterone enanthate were used to increase androgen. The proposed K02 Award will allow the PI to devote the majority of his time to investigating the behavioral, neuroendocrine, and cognitive consequences of these alterations in prenatal androgen exposure in socially-living rhesus monkeys. These studies will provide fundamental information about how early hormone exposure affects the development of sexual and sex-typed behavior in a primate with a complex social organization and a long period of sexual development. One of the most striking human cognitive sex differences is in aspects of spatial cognition. The proposed support will allow the PI to develop computerized approaches to studying spatial cognition in group-living monkeys to take advantage of a large sample of rhesus monkeys with atypical androgen exposure created during the previous funding period. In addition, the increased time available for research will allow investigation of possible sex differences in brain structure using magnetic resonance imaging. If neuroanatomical sex differences are demonstrated they can then be pursued in the experimental subjects as they near adult development. During the term of this award the experimental and control subjects will go through puberty and enter adulthood. A goal of the proposed plan is to explore how alterations in the prenatal androgen environment affect the process of pubertal change and adult reproductive behavior. Because none of our hormonal treatments substantially altered the genitalia of experimental females there are no apparent physical barriers to pregnancy. It will be particularly interesting to determine whether substantially less drastic alterations in prenatal androgen exposure than those previously used produce marked changes in reproductive and maternal behavior. In males that have experienced reduced prenatal androgen exposure the PI will determine whether the timing of such hormonal alterations differentially affects their sexual behavior. These studies of nonhuman primates have particular relevance to issues of human gender development, particularly the occurrence of gender dysphoria. The last goal of the proposal is to allow the PI to gain a deeper understanding of human gender dysphoria by spending time at the Clarke Institute of Psychiatry in Toronto Canada, which has one of the world's most active research and treatment programs for childhood and adult gender dysphoria. The combination of these efforts will allow the PI to expand his research into new areas, while increasing his understanding of its relevance to important human mental health conditions.
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