NEUROENDOCRINE EFFECTS OF PRENATAL EXPOSURE TO ALCOHOL

产前接触酒精对神经内分泌的影响

• 批准号: 3112814
• 负责人: PATRICIA M RODIER
• 金额: $ 23.01万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3112814
• 关键词: alcoholic beverage consumption; animal puberty; endocrine disorder; estrus; fertility; fetal alcohol syndrome; follicle stimulating hormone; gonads; growth hormone releasing hormone; histology; hypothalamus; laboratory rat; luteinizing hormone; neuroanatomy; neuroendocrine system; pituitary gland; postnatal growth disorder; prenatal stress; radioimmunoassay; sex development disorder; somatostatin; testis; tissue /cell culture

Alcohol is a teratogen known to cause extensive damage to the brain, yet its effects on the neuroendocrine control of growth and reproduction have not been investigated. The hypothesis that the hypothalamic-pituitary axis may be injured by prenatal exposure is supported only by evidence of postnatal growth deficiencies in human and animal FAS, and by a few reports of delays or changes in sexual maturation, but a vigorous test of the hypothesis is warranted, because endocrine deficiencies are treatable, unlike most of the symptoms of prenatal injury. Using a different teratogen, we have demonstrated changes in the hypothalamus and pituitary, and in the postnatal growth rate of rats exposed in utero. Based on these studies, and studies of the hypothalamic control of the reproductive system, we propose to compare offspring of rats exposed to chronic 35% ethanol-derived calories with isocaloric controls on the following measures: a) The number of growth hormone releasing factor (GRF) neurons, somatotropin release inhibiting factor (SRIF) neurons, and the number of luteinizing hormone releasing hormone (LHRH) neurons in the hypothalamus. The number and activity of these cells is related to the pituitary release of growth hormone, luteinizing hormone, and follicle stimulating hormone. b) The size and immunohistochemical composition of the anterior pituitary, where the somatotropic and gonadotrophic cells produce their hormones. c) The average circulating levels of growth hormone an luteinizing hormone, and the response of each to stimulation of the pituitary. d) The pattern of postnatal growth from birth to 60 days. e) The age of puberty, as judged by vaginal patency and estrous cyclicity in females, and by testis descent in males. f) The histological development of the male and female gonad at 4, 35, and 60 days. While these measures will not assay every way in which the systems could be deficient, they will evaluate the most likely symptoms and sources of endocrine disturbances, filling a crucial gap in the FAS literature, and, perhaps, suggesting clinical solutions to some features of the syndrome.

酒精是一种致畸剂，已知会对大脑造成广泛损害，但 它对生长和生殖的神经内分泌控制的影响 没有被调查。 假设下丘脑-垂体轴 可能因产前暴露而受伤仅由以下证据支持 人类和动物 FAS 的产后生长缺陷，以及一些报告 性成熟的延迟或改变，而是对性成熟的严格测试 假设是有道理的，因为内分泌缺陷是可以治疗的， 与大多数产前损伤的症状不同。 使用不同的 致畸剂，我们已经证明了下丘脑和垂体的变化， 以及子宫内暴露的大鼠的产后生长率。 基于这些 下丘脑控制生殖的研究 系统中，我们建议比较暴露于慢性 35% 的大鼠的后代 乙醇衍生的热量，并在以下方面进行等热量控制 措施： a) 生长激素释放因子（GRF）神经元的数量， 生长激素释放抑制因子（SRIF）神经元，以及数量 下丘脑中的黄体生成素释放激素（LHRH）神经元。 这些细胞的数量和活性与垂体释放有关 生长激素、黄体生成激素和卵泡刺激素。 b) 垂体前叶的大小和免疫组织化学组成， 生长激素和促性腺细胞产生激素的地方。 c) 生长激素和促黄体激素的平均循环水平 激素，以及每种激素对垂体刺激的反应。 d) 从出生到60天的产后生长模式。 e) 青春期的年龄，通过阴道通畅和动情周期来判断 在女性中，通过睾丸下降在男性中。 f) 4、35 和 3 岁时男性和女性性腺的组织学发育 60 天。 虽然这些措施不会分析系统可能采用的所有方式 缺乏，他们将评估最可能的症状和来源 内分泌紊乱，填补了 FAS 文献中的一个重要空白，并且， 或许，可以针对该综合征的某些特征提出临床解决方案。