IMPACT OF ETHANOL ON FEMALE RODENT REPRODUCTION

当过量使用时，乙醇(乙醇)是一种主要的滥用药物 对男性和女性的下丘脑-垂体腺有有害的影响- 性腺轴。这种现象的分子和细胞机制细节 我们的实验室已经并正在深入研究这些影响 雄鼠体内的其他基因。然而，与之形成鲜明对比的是， 酒精对下丘脑-垂体-脑组织影响的深入研究很少。 成年、青春期后雌性大鼠的性腺轴。这样做的研究 EXist表明，乙醇也有很强的作用。 需要检验的具体假设是：急性和慢性酒精 用药通过减少稳定状态来扰乱发情周期 下丘脑促黄体生成素释放激素原水平 通过抑制原LHRH向生物活性LHRH的转化。 这会导致垂体促性腺激素衰竭和继发性性腺 失败了。 证明或驳斥这一假设的数据将在以下过程中获得 实现两个具体目标。 A.在发情周期的每一天，确定单一的 IP注射乙醇(与IP生理盐水比较)对前ProLHRH基因的影响 表达(通过逆转录/聚合酶链式反应)，proLHRH 成熟生物活性LHRH十肽的加工(放射免疫法) 针对前体或产物的抗体)，脑下垂体 促性腺激素基因表达(Northern分析)，含量，血清 促性腺激素水平与卵巢重量、组织学和激素功能 (根据血清雌二醇和孕酮以及子宫重量和 组织学)(实验1)。 B.确定两个月喂食液体乙醇的效果 含日粮(与配对饲喂液体对照日粮相比)相同 参数与具体目标A(实验2)相同。 在第一个实验中，单次ip无水乙醇(或生理盐水对照) 将于下午1：00举行。在发情周期的每一天。此后， 动物将在3、4、5、6、7和9点的发情日被宰杀。在……里面 以捕捉黄体生成素和卵泡刺激素的发情高峰。在接下来的几天里 发情周期，下午1点注射乙醇后，动物将 只在下午4点被杀。在实验2中，牺牲时间将是相似的 与实验1中的那些相比。

When used in excess quantities, ethanol (ETOH) is a major drug of abuse with deleterious effects on the male and female hypothalamic-pituitary- gonadal axis. The molecular and cellular mechanistic details of such effects have been and are being studied intensively by our laboratory and others in the male rat. In contrast, however, there has been relatively little in depth study of ethanol's effects on the hypothalamic-pituitary- gonadal axis of the adult, post-pubertal female rat. The studies that do exist suggest that there is a potent effect of ETOH as well. The specific hypothesis to be tested is: ACUTE AND CHRONIC ETHANOL ADMINISTRATION DISRUPTS THE ESTROUS CYCLE BY DIMINISHING STEADY STATE LEVELS OF HYPOTHALAMUS PRE-PRO LUTEINIZING HORMONE RELEASING HORMONE (LHRH) mRNA AND BY IMPAIRING CONVERSION OF PRO LHRH TO BIOACTIVE LHRH. THIS LEADS TO PITUITARY GONADOTROPIN FAILURE AND SECONDARY GONADAL FAILURE. Data to prove or refute this hypothesis will be obtained in the course of accomplishing TWO specific aims. A. To determine on each day of the estrous cycle the effect of a single IP injection of ethanol (compared to IP saline) on pre-proLHRH gene expression (by reverse transcription/polymerase chain reaction), proLHRH processing to the mature bioactive LHRH decapeptide (by RIA with antibodies specific for either precursor or product), pituitary gonadotropin gene expression (by Northern analysis), and content, serum gonadotropin levels, and ovarian weight, histology and hormonal function (as assessed by serum estradiol and progesterone and uterine weight and histology) (Experiment 1). B. To determine the effects of two months of feeding of a liquid ETOH containing diet (compared to pair fed liquid control diet) on the same parameters as in Specific Aim A (Experiment 2). In the first experiment, a single IP injection of ETOH (or saline control) will be given at 1:00 p.m. on each day of the estrous cycle. Thereafter, animals will be sacrificed on proestrous at 3, 4, 5, 6, 7 and 9 p.m. in order to capture the proestrous surge of LH and FSH. On other days of the estrous cycle, after ethanol injection at 1:00 p.m., animals will be killed only at 4:00 p.m. In Experiment 2, sacrifice times will be similar to those in Experiment 1.