INTERACTION OF ALCOHOL AND THE HPT-AXIS

酒精和 HPT 轴的相互作用

• 批准号: 3111711
• 负责人: GEORGE A MASON
• 金额: $ 12.4万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3111711
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; alcoholism /alcohol abuse prevention; alcoholism /alcohol abuse therapy; drug withdrawal; hormone metabolism; hormone receptor; hypothalamic pituitary axis; laboratory rat; thyroid function; thyrotropin; thyrotropin releasing hormone

APPLICANT'S ABSTRACT: This revised proposal is to investigate the interactions of alcohol consumption and Hypothalamic-pituitary-thyroid (HPT)-axis function in rats. Measures of HPT-axis function including thyroid hormones, TSH and TSH response to TRH are altered in alcoholics - a tendency to incur certain of these changes may be inherited and may contribute to the development of alcoholism. In some studies using rats, changes in HPT-axis measures similar to those reported in alcoholics have been induced by chronic alcohol ingestion, and thyroid status has been shown in some studies to influence voluntary alcohol consumption. However, a clear picture has not emerged, in part because much of the previous work lacked adequate controls for differences in nutrition, metabolism, conditioning and associated variables. Presently, the concept that alcohol abuse alters HPT-axis function and that drinking behavior is influenced by HPT-axis function have not been adequately developed (or tested) and therefore can offer little insight toward the prevention and treatment of alcoholism. Two research strategies will be followed: 1) to determine how chronic alcohol exposure changes HPT-axis function and 2) to determine how an altered HPT-axis such as occurs in hypothyroidism, affects voluntary alcohol consumption. Specifically, the effects of acute, chronic and chronic intermittent alcohol, and acute and chronic withdrawal from chronic alcohol in 1) T3, T4, rT3, TSH, TSH response to TRH in blood serum, 2) T3, T4, rT3 and TRH in brain and 3) TRH receptors in pituitary and brain, will be determined. The contributing roles of alcohol and thyroid hormones metabolism in altering HPT-axis function will be ascertained. The effects of centrally and peripherally administered thyroid hormones and TRH and centrally administered Fab fragments from antisera to T3, T4 and TRH on voluntary alcohol consumption will also be examined. These preclinical studies may help to identify HPT-axis conditions in man which increase susceptibility to develop alcoholism and thereby identify novel strategies for prevention and even treatment of alcoholism.

申请人摘要：本修订提案旨在调查 饮酒与下丘脑-垂体-甲状腺的相互作用 （HPT）轴功能。 HPT轴功能的测量，包括 酗酒者的甲状腺激素、促甲状腺激素和促甲状腺激素对促甲状腺激素释放激素的反应发生改变， 引起这些变化的倾向可能是遗传的， 有助于酒精中毒的发展。 在一些使用老鼠的研究中， HPT轴测量的变化与酗酒者报告的相似， 是由慢性酒精摄入引起的，甲状腺状态一直是 在一些研究中显示，这会影响自愿饮酒。 然而，在这方面， 一个清晰的画面还没有出现，部分原因是以前的工作 缺乏对营养、新陈代谢、 条件和相关变量。 目前，酒精的概念 滥用改变了HPT轴功能，饮酒行为受 HPT轴功能尚未充分开发（或测试）， 因此，对预防和治疗 酒精中毒 两个研究策略将遵循：1）确定如何慢性 酒精暴露会改变HPT轴功能，2）确定 改变的HPT轴，如发生在甲状腺功能减退症，影响自愿 酒精消费。 具体而言，急性、慢性和 慢性间歇性酒精，以及急性和慢性戒断 1）T3、T4、rT 3、TSH、TSH对血清中TRH的反应，2）T3， 脑内T_4、rT_3和TRH受体及垂体和脑内TRH受体， 被确定。 酒精和甲状腺激素的作用 将确定代谢在改变HPT轴功能中的作用。 的影响 中枢和外周给予甲状腺激素和TRH， 集中给予来自T3、T4和TRH抗血清的Fab片段， 自愿饮酒也将受到审查。 这些临床前 研究可能有助于确定人类的HPT轴条件， 从而确定新的策略 预防甚至治疗酒精中毒。