This project 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 differentiation 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 30 days starting on gestational day 40 or 110. Mothers of male fetuses will be treated with a androgen receptor blocker (flutamide) or vehicle starting at the same times and for the same duration as the female treatments. Prenatal flutamide will block androgen 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 maternal 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. The concurrent collection of behavioral, endocrine, and somatic data on both males and females in a socially complex environment will produce a valuable data set for assessing the impact of prenatal androgen upon somatic and psychological development and make these studies relevant to issues of human gender development and under discordance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH050268-03
Application #
2033979
Study Section
Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
Project Start
1994-12-01
Project End
1999-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Emory University
Department
Biology
Type
Other Domestic Higher Education
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Forger, Nancy G; Ruszkowski, Elara; Jacobs, Andrew et al. (2018) Effects of sex and prenatal androgen manipulations on Onuf's nucleus of rhesus macaques. Horm Behav 100:39-46
Stephens, Shannon B Z; Raper, Jessica; Bachevalier, Jocelyne et al. (2015) Neonatal amygdala lesions advance pubertal timing in female rhesus macaques. Psychoneuroendocrinology 51:307-17
Raper, Jessica; Stephens, Shannon B Z; Sanchez, Mar et al. (2014) Neonatal amygdala lesions alter mother-infant interactions in rhesus monkeys living in a species-typical social environment. Dev Psychobiol 56:1711-22
Goursaud, Anne-Pierre S; Wallen, Kim; Bachevalier, Jocelyne (2014) Mother recognition and preference after neonatal amygdala lesions in rhesus macaques (Macaca mulatta) raised in a semi-naturalistic environment. Dev Psychobiol 56:1723-34
Raper, Jessica; Stephens, Shannon B Z; Henry, Amy et al. (2014) Neonatal amygdala lesions lead to increased activity of brain CRF systems and hypothalamic-pituitary-adrenal axis of juvenile rhesus monkeys. J Neurosci 34:11452-60
Raper, Jessica; Wallen, Kim; Sanchez, Mar M et al. (2013) Sex-dependent role of the amygdala in the development of emotional and neuroendocrine reactivity to threatening stimuli in infant and juvenile rhesus monkeys. Horm Behav 63:646-58
Raper, Jessica; Wilson, Mark; Sanchez, Mar et al. (2013) Pervasive alterations of emotional and neuroendocrine responses to an acute stressor after neonatal amygdala lesions in rhesus monkeys. Psychoneuroendocrinology 38:1021-35
Raper, Jessica; Bachevalier, Jocelyne; Wallen, Kim et al. (2013) Neonatal amygdala lesions alter basal cortisol levels in infant rhesus monkeys. Psychoneuroendocrinology 38:818-29
Stephens, Shannon B Z; Wallen, Kim (2013) Environmental and social influences on neuroendocrine puberty and behavior in macaques and other nonhuman primates. Horm Behav 64:226-39
Wallen, Kim; Lloyd, Elisabeth A (2011) Female sexual arousal: genital anatomy and orgasm in intercourse. Horm Behav 59:780-92

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