Experimental results show that the volume of the sexully dimorphic nucleus of the preoptic area (SDN-POA) is reduced in male rats exposed to ethanol in utero. The alteration in the structure of this nucleus possibly is related to a biochemical mechanism during a critical period in brain development due to perinatal ethanol exposure which has lasting effects in the adult animal. The primary objective is to determine the effects of in utero ethanol exposure on central regulation of reproductive function of male and female rats resulting from alterations in preoptic area structure. Experiments will focus upon the function of the hypothalamo-hypophyseal-gonadal axis. The effect of in utero ethanol exposure on hypothalamic content of luteininzing hormone releasing hormone (LHRH) and the correlation of hypothalamic neurotransmitter content and turnover relative to LHRH synthesis and secretion will be determined. Anterior pituitary function will be determined by examination of the gonadotrophin content and release from the pituity both in vivo and in vitro. Gonadal function will be detemined by the examination of gonadal steroid synthesis and secretion in male and female rats. The effect of in utero ethanol exposure on steroid feedback inhibition of hypothalamic LHRH will be determined by examination of hypothalamic steroid binding, hypothalamic neurotransmitter response to gonadal steroids and the ability of gonadal steroids to induce gonadotrophin inhibition. In each experiment pregnant rats will be fed either a laboratory chow diet ad libitum, a liquid diet contaning ethanol (5% w/v), or a liquid diet in which maltose-dextrins have been isocalorically substituted for the ethanol. The offspring will be examined for the effects of in utero alcohol exposure on neuroendocrine function. Radioimmunoassay of gonadotrophins in the pituitary and serum, and LHRH in the preoptic area and hypothalamus will be made. High pressure liquid chromatography (HPLC) with electrochemical detection will be used for measuring hypothalamic catecholamine content and turnover. HPLC will also be used to determine gonadal and serum steroid concentrations. Preoptic area steroid cytosolic binding will be determined by using radioligand binding techniques. Alterations in the regulation of reproduction in response to morphological, biochemical and physiological changes in this area of the central nervous system can be examined following in utero ethanol exposure. A definitive investigation of the effects of in utero ethanol exposure upon reproductive function would be pertinent to the understanding and possible treatment of individuals who now suffer from fetal ethanol exposure and who are entering child bearing age.
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