During human adolescence the brain undergoes a profound remodeling that is both sculpted by gonadal steroid hormones and associated with the emergence of sex-biased psychopathologics such as anorexia nervosa, depression, and schizophrenia. Because puberty is a period of extraordinarily rapid change in the nervous system, the brain may be particularly vulnerable to perturbations in the timing of interactions between hormones and developmental trajectory. The normal timing of these interactions in human adolescents is altered by anabolic steroid use, by the increasingly earlier onset of gonadal puberty in girls, and by the delay in gonadal maturation induced by eating disorders, extreme exercise, or disease. The overall goal of this research is to determine how the timing of interactions between the rapidly developing adolescent brain and gonadal steroid hormones influences individual differences adult behavior and nervous system structure. Using a rodent model, we've found that the absence of gonadal hormones during pubertal brain development adversely affects the expression of male social behaviors in adulthood. These behavioral compromises are long-lasting, and are not reversed by testosterone replacement in adulthood, indicating that the timing of exposure to steroid hormones determines adult responses to hormonal and sensory stimuli.
The specific aims of the proposed work are to 1) test the hypothesis that capacity for testosterone-dependent organization of reproductive behavior varies over prepubertal, pubertal, and postpubertal development; 2) discover whether androgenic or estrogenic actions of testosterone mediate testosterone-dependent organization of neural circuits and behavior during puberty; and 3) test the hypothesis that steroid-dependent pubertal organization of male reproductive behavior is associated with enduring structural modifications within the neural circuit mediating the behavior. The strategy will be to vary the postnatal age at which male hamsters are exposed to a three week period of androgen or estrogen (either before, during, or after puberty), and then assess behavior and structural characteristics in adulthood. This research integrates neuroanatomy, endocrinology, and behavior, and will establish new and fundamental principles of developmental neurobiology and psychobiology that are directly relevant to human development and mental health.
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