Abuse of anabolic steroids (androgens) by athletes is of increasing concern to society. It is estimated that one million athletes in this country may use or abuse androgens. The effects of these massive doses of androgens on the brain have not been studied. The long-term goal of these studies is to gain insight into the actions of steroids of abuse on the central nervous system. The following specific aims are proposed. 1. Determination of effects of physiological and pharmacological levels of natural and synthetic androgens on neuropeptide gene expression in different brain regions and in the pituitary. 2. Determination of whether the effects of pharmacological levels of synthetic androgens are mediated through androgen receptors, estrogen receptors, glucocorticoid receptors and/or opiate receptors. 3. Examination of the neuroendocrine effects of pharmacological levels of synthetic androgens. 4. Development of antibodies to the androgen receptor. 5. Use of antibodies to the androgen receptor for localization and characterization of neurons with androgen receptor immunoreactivity. 6. Examination of the possibility that pharmacological levels of synthetic androgens regulate brain or pituitary levels of receptors for androgen, estrogen, progesterone, or glucocorticoids. Methods include a) determination of neuropeptide mRNA levels by filter and in situ hybridization, b) determination of circulating hormone levels by radioimmunoassay, c) characterization of antibodies by Western blots, immunoprecipitation and immunocytochemistry, d) characterization of neurons with androgen receptor immunoreactivity by double immunocytochemistry, e) determination of steroid receptor immunoreactivity levels by ELISA. These studies should provide essential information on effects of abused androgens on the rat brain, and thus may serve as a guide to further investigations into actions of these steroids on the human nervous system.
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