Prenatal androgens influence the development of male sex-typical behavior and neuroendocrine function. Disease states or environmental conditions which interfere with fetal production or action of androgens can permanently alter the life-span development of male monkeys. Similarly, accidental exposure of genetic females to androgens alters their sex-typical development. Evidence suggests that prenatal androgens may produce behavioral change by modifying brain development at developmentally different times than they alter external reproductive anatomy. This project investigated the possibility that exposing genetic females to prenatal androgen at different times during gestation and at doses likely to be accidentally encountered could modify female-typical behavioral and neuroendocrine development without markedly altering external reproductive anatomy. In a complementary manner, we briefly interrupted endogenous androgen action in fetal males with and androgen receptor blocker (flutamide) to mimic the possible short-term effects of immune system activation of exposure to environmental hormone agonists which might suppress testicular function through negative feedback. Forty three timed-mated females received either testosterone enanthate (TE, 20mg/week for 4 weeks), flutamide (FL, 30mg/kg BW twice daily in DMSO for 30 days), or vehicle starting on gestational day 30 or 110. A total of 35 offspring were delivered (20 females and 13 males). Prenatal FL treatment starting on GD 30 (early treatment) markedly altered the reproductive anatomy of the two males successfully treated in a female-like direction. Flutamide treatment starting on GD 110 (late treatment) had no apparent effect on male reproductive anatomy, but did affect neonatal androgen secretion as these males had significantly higher postnatal T secretion than either early-treated flutamide males or control males. Prenatal treatments modified female reproductive anatomy, with early flutami de treatment having the most marked effect. TE treatment had no measurable effect on female reproductive anatomy, but early FL modified the anatomy in a manner that has been shown in humans to indicate reduced androgen exposure. In addition, early FL females showed a significantly increased LH response to exogenous GnRH at 2mo of age in comparison to control or prenatally androgen treated females. These findings suggest that genetic females are naturally exposed prenatally to amounts of androgen insufficient to markedly masculinize their external reproductive anatomy, but which exert subtle, but significant effects on both anatomical and neuroendocrine development. Such findings have important implications for understanding both natural variation in female neuroendocrine function as well as in the assessment of the effects of exposure to environmental hormone agonists.
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