Alcohol abuse and alcohol dependence are the 4th most common psychiatric disorders reported by young women (18-24) according to an NIMH survey. A broad spectrum of reproductive system disorders (e.g. amenorrhea, anovulation, luteal phase dysfunction, ovarian pathology, and hyperprolactinemia) are associated with alcohol abuse and the underlying mechanisms are unknown. We propose to continue research on the neuroendocrine correlates of alcohol- induced menstrual cycle abnormalities. The primate model permits systematic evaluation of neuroendocrine hormones before, during and after induction of alcohol dependence without the confounding influence of polydrug abuse or medical disorders. Since amenorrhea and other infertility disorders often are characterized by abnormal gonadotropin secretory patterns, we propose to study the effects of chronic alcohol self-administration and withdrawal on LH and FSH pulse frequency and amplitude. Parallel studies of the covariance between alcohol-induced changes in ACTH and cortisol and LH and prolactin are planned because gonadotropin pulse frequency is also modulated by the hypothalamic- pituitary-adrenal axis. One goal is to examine possible mechanisms underlying luteal phase dysfunction by determining if alcohol stimulates ovarian steroid hormones (estradiol, progesterone) and non-steroidal ovarian peptides (inhibin) in a way that could account for alcohol-induced suppression of follicular FSH. The acute effects of alcohol on ovarian function will also be evaluated with hCG. The hormonal milieu of early pregnancy will be simulated by daily administration of ascending doses of hCG and the effects of alcohol intoxication on ovarian hormones will be examined. Over 28% of American women are peri- and post-menopausal, yet little is known about alcohol's effects o hypothalamic-pituitary- adrenal function after menopause. We propose to study the effects of alcohol on LH, prolactin and estrogens (derived from non-ovarian sources) in the ovariectomized model of menopause. An alcohol- related change in gonadal and adrenal steroid levels could alter the health risks and benefits associated with steroid replacement therapies for menopause. Plasma hormone levels will be measured with standard radioimmunoassay procedures; gonadotropin secretory patterns will be analyzed with computerized techniques; and operant behavioral procedures will be used to induce alcohol self- administration and dependence in the primate model of alcoholism.
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