Xenoestrogens are chemicals with diverse structure that mimic or interfere with the action of endogenous estrogens. Two compounds, bisphenol A (BPA) and octylphenol (OP), are the focus of this proposal. These compounds are abundant in the environment, bind to the estrogen receptor (ER) and act as partial estrogen agonists. Studies from our laboratory and others revealed that both affect pituitary hormone secretion and reproductive tract growth and morphology and their in vivo bioactivity is higher than expected from their weak in vitro binding affinity. Whether BPA or OP promote developmental abnormalities in the neuroendocrine system that result in reduced fertility, has not been investigated. We propose to use the neuroendocrine axis that regulates prolactin (PRL) secretion as a model system for addressing the following questions: a) do xenoestrogens, given to early neonatal rats before the final maturation of their regulatory apparatus, induce alterations in the pattern of PRL release, onset of puberty or estrous cyclicity?, and b) do these alterations result from changes at the level of the hypothalamus, pituitary or both? Specific Aims: To determine the effects of exposing female Fischer 344 (F344) pups to BPA or OP on days 1-5 after birth on: a) serum PRL levels on days 10-40 of life, b) onset of puberty, estrous cyclicity and ovulation rate, c) tyrosin hydroxylase (TH) expression/activity in the hypothalamus, d) D2-dopamine receptor (D2R) expression/binding in the pituitary, and e) ERalpha and ERbeta expression/regulation in both the hypothalamus and the pituitary. The results of this research should provide a much needed experimental foundation for assessing the vulnerability of the developing neuroendocrine system to insults by environmental factors.
