The objective of this research is to elucidate the neural mechanisms by which gonadal hormones affect behavior in male and female primates during development. During the fetal period in monkeys and man, the testes undergo a phase of marked secretory activity, whereas the fetal ovaries are relatively quiescent. This testosterone has been shown to exert organizing effects on behavior and on genital target tissues during sensitive periods of fetal and neonatal development. These effects may underlie sexual dimorphisms in the brain and contribute to later differencs in social, sexual and aggressive behaviors. Testosterone is enzymatically converted to estradiol and dihydrotestosterone in target neurons, and the role of estrogenic and androgenic metabolites in the many actions of testosterone is not completely understood. Although there are data on the localization of target neurons for gonadal steroids in adult primates, similar information for the early developmental period is completely lacking, but it has great relevance for an understanding of the ontogeny of aggression and for other sexually dimorphic behaviors and cognitive abilities, including those processes that underlie sexual differentiation and the development of gender identity in the human. The studies in male and female rhesus monkeys will use thaw-mount autoradiogrphy to map precisely the locations of target cells in brain, pituitary, and peripheral target tissues following the in vivo injection of 3H-testosterone, 3H-dihydrotestosterone, 3H-estradiol, and 3H-ORG 2058 (a synthetic progestin receptor ligand). Studies in fetal animals will be performed at 65-70, 80-84 and 110-114 days of gestation. The influence of endogenous hormones on the uptake of radioactivity following 3H-testosterone injection will be investigated by comparing intact and gonadectomized fetuses. In parallel studies, high performance liquid chromatography will be used to help characterize the labeled metabolites that accumulate in nuclei of target cells after the administration of 3H-testosterone. Other autoradiographic and HPLC studies will be conducted in neonatal males and females at 3 days and 4 weeks of age. The results of these studies may help to provide the first identification and localization in primates of the anatomical substrate for the organizing effects of gonadal steroids on sexually dimorphic behaviors and on neuroendocrine regulation, and may help identify sex differences in the brain during fetal and neonatal development.
