This is a request for an ADAMHA RSDA Level II award. The research investigates gender development in group-living male and female rhesus monkeys exposed to atypical levels of prenatal androgen. These studies will elucidate the role that prenatal androgens play in regulating genital and psychological differentiation in a primate, under social conditions that produce a full range of gender-related social and sexual behavior. By employing short-term treatments during early and late gestation the project seeks to separate the effects of prenatal androgen on masculinization of the genitalia from its effects upon masculinization and defeminization of behavior. These studies are relevant to issues of human gender differentiations and discordances between genital sex and gender role behavior, a clinical problem that affects a substantial number of humans. To achieve these goals, time-mated pregnant rhesus females, living in large age-graded heterosexual groups, will have the sex of their fetus identified using sex chromatin staining. Mothers of female fetuses will be injected with testosterone enanthate (TE) or vehicle for 35 days starting on gestational day 40 or 110. Mothers of male fetuses will be injected with a Nal-Lys GnRH antagonist (Antide), Antide plus TE, or vehicle starting at the same times and for the same duration as the female treatments. Prenatal Antide will suppress testicular function creating males who are androgen deficient for a brief period early or late in gestation. The times selected represent periods during or after genital masculinization and when previous work has shown androgens to differentially affect the sexually dimorphic patterns of rough play and juvenile mounting. Experimental and control animals will be observed behaviorally from birth through the transition into adulthood using methodology that captures traditional sexually dimorphic patterns of behavior and additional patterns of social behavior that are only observable when infants can interact with all ages and sexes in an unrestricted manner. Endocrine and skeletal development will be tracked with systematic collection of serum samples to measure neonatal and peripubertal patterns of hormone secretion and morphometric measures of skeletal growth. Pituitary function will be challenged with exogenous GnRH at several times during development to assess the effects of early androgen exposure on the integrity of the hypothalamo-pituitary-gonadal axis. After the pubertal transition, male and female sexual behavior will be investigated in response to their endogenous hormones. If experimental females produce offspring, the relationship between early androgen exposure and materna] behavior will be investigated. These studies provide the first experimental manipulation of prenatal androgen in male primates and will substantially extend our understanding of the role androgen plays in gender differentiation in primates. RSDA support will free the PI from teaching and administrative duties and allow the development of new behavioral and diagnostic techniques for assessing the effects of prenatal androgen manipulations.
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