EFFECTS OF ALCOHOL ON HUMAN OVARIAN CELL FUNCTION

女性酒精中毒导致生殖系统显著畸变 功能，如闭经，痛经，不排卵，不孕， 黄体期缺陷，绝经期提前和自发性流产率增加 堕胎 这些变化中只有一部分似乎是可逆的。 最近 数据表明，生殖系统功能障碍也观察到非 酗酒的女性 尽管数据显示， 乙醇可能对下丘脑垂体轴产生有害影响， 或卵巢，酒精中毒的部位和机制， 生殖系统知之甚少。 拟议研究的长期目标是了解 酒精对卵巢的毒性机制。 先前的研究表明， 慢性酒精中毒可能会导致严重的卵巢功能障碍， 形态学变化，导致类固醇激素减少 分泌，这些影响可能会引起大部分的生殖 乙醇的毒性 了解酒精的生殖毒性 在分子水平上发挥作用，必须开发适合于 体外模型 最近，一种组织培养系统， 叶黄素（LG）细胞暴露于恒定的“生理”浓度的 乙醇已经开发出来了。 在该系统中，乙醇选择性抑制 LH对类固醇生成的刺激作用。 该系统将用于 探讨乙醇对人LG细胞的直接毒性机制， 人类卵巢细胞 计划的实验如下： 乙醇对LH受体数量和亲和力的影响 LH受体数量与LH受体的结合和独立评价 抗体，乙醇对LH受体的作用，鸟嘌呤结合蛋白（G 蛋白质）相互作用和乙醇对G蛋白偶联的影响， 腺苷酸环化酶 由于LH可能通过 Ca++/磷酸肌醇/二酰甘油/蛋白激酶C途径，作用 将测量该系统组件上的乙醇，以确定是否 乙醇可通过该途径调节LH的生理效应。 培养的 将开发大鼠LG细胞模型，以尝试和复制 酒精对人类LG细胞的影响，从这些研究中，我们希望建立 酒精作为一种直接的性腺毒素的机制。

Alcoholism in women leads to significant aberrations in reproductive system function such as, amenorrhea, dysmenorrhea, anovulation, infertility, luteal phase defects, earlier menopause and increased rates of spontaneous abortions. Only some of these changes appear to be reversible. Recent data suggest that reproductive system dysfunction is also observed in non alcoholic women who are alcohol abusers. Even though data suggest the ethanol may exert detrimental effects on the hypothalmopituitary axis and or the ovary, the site(s) and mechanisms(s) of alcohol toxicity on the reproductive tract are poorly understood. The long term objectives of the proposed research are to understand the mechanisms of alcohol toxicity on the ovary. Previous research indicated that chronic alcoholism may produce significant ovarian dysfunction and morphological changes with consequent decreases in steroid hormone secretion, and these effects may give rise to much of the reproductive toxicity of ethanol. To understand the toxicity of alcohol on reproductive function at the molecular level it is imperative to develop suitable in vitro models. Recently a tissue culture system where human granulosa lutein (LG) cells are exposed to constant "physiological" concentrations of ethanol has been developed. In this system ethanol selectively inhibited stimulatory effects of LH on steroidogenesis. This system will be used to study the mechanism of toxicity of ethanol directly on human LG cells and human ovarian cells. Planned experiments are the following; studies of ethanol action on LH receptor number and affinity using iodo hormone binding and independent evaluation of LH receptor number with LH receptor antibodies, alcohol action on LH receptor, guanine binding protein (G protein) interactions and effects of ethanol on G protein coupling to adenylate cyclase. Since LH may act on steroidogenesis via the Ca++/inositol phosphate/diacylglycerol/protein kinase C pathway, actions of ethanol on components of this system will be measured to determine whether ethanol can modulate LH's physiologic effects via this pathway. A cultured rat LG cell model will be developed to try and duplicate the effects of alcohol on human LG cells and from these studies we hope to establish the mechanisms by which alcohol acts as a direct gonadal toxin.