MECHANISMS OF ALCOHOLS EFFECTS ON BONE METABOLISM

酒精影响骨代谢的机制

• 批准号: 2841999
• 负责人: KATHERINE M KEIVER
• 金额: $ 5万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2841999
• 关键词: 1,25 dihydroxycholecalciferol; alcoholic beverage consumption; atomic absorption spectrometry; blood chemistry; bone density; bone development disorder; bone metabolism; calcium metabolism; embryo /fetus toxicology; ethanol; gastrointestinal nutrient absorption; hormone regulation /control mechanism; laboratory rat; parathyroid hormone related protein; parathyroid hormones; photon absorptiometry; pregnancy; vitamin metabolism

Alcohol has deleterious effects on the bone of adult and developing animals. Previous work in our lab has shown that chronic alcohol intake during pregnancy in the rat reduces birth weight and retards fetal skeletal development. In addition we have shown that alcohol consumption has adverse effects on bone of the pregnant female herself. Importantly, our studies show that alcohol impairs the ability of the pregnant dam and fetus to regulate their Ca metabolism. Fetal life and pregnancy are both periods in which bone is vulnerable to alcohol's adverse effects due to the growth and development of the fetal skeleton and the increased Ca required by the dam to support its mineralization. In the present proposal, we will expand our studies on the pregnant female and the fetus to investigate further the effects of alcohol on Ca regulation and bone. Our Specific Aims are to determine: 1) the mechanisms underlying the impaired Ca regulation of pregnant rats consuming alcohol; and 2) if the effect of alcohol on fetal growth and skeletal development results from the inability of the dam to regulate her blood iCa levels. Specific Aim 1 will test the hypotheses that alcohol interferes with the ability of the pregnant rat to increase serum levels of PTH and 1,25(OH)2D in response to a decrease in blood iCa levels, resulting in a) a lack of increase in Ca reabsorption by the kidney, b) a failure to increase intestinal Ca absorption, and c) an inability to mobilize adequate Ca from bone. Specific Aim 2 will test the hypotheses that the decrease in maternal blood iCa levels retards fetal growth and skeletal development by causing a decrease in fetal blood iCa levels, which may a) inhibit bone formation directly, or b) trigger a compensatory response by the fetus, such as an increase in secretion of parathyroid hormone related peptide (PTHrP) or parathyroid hormone (PTH), which may in turn inhibit bone formation. The proposed studies will begin to elucidate mechanisms underlying the effects of alcohol on bone during 2 periods in which bone mass is vulnerable to perturbation: pregnancy and fetal development. Alcohol-induced perturbations in bone mass may have significant implications for the development of osteoporosis, which is a major health care issue today.

酒精对成人的骨骼和发展有害 动物。 我们实验室的先前工作表明慢性酒精摄入量 大鼠怀孕期间减轻了出生体重并阻碍胎儿 骨骼发育。 另外，我们已经表明酒精 消费对怀孕女性的骨骼产生不利影响。 重要的是，我们的研究表明，酒精会损害 怀孕的大坝和胎儿调节其CA代谢。 胎儿的生活和 怀孕都是骨头容易受到酒精的时期 由于胎儿骨骼的生长和发展而产生的不利影响 大坝需要增加的CA来支持其矿化。 在本提案中，我们将扩大有关怀孕的研究 女性和胎儿进一步研究酒精的影响 CA调节和骨头。 我们的具体目的是确定：1​​） 孕妇大鼠CA调节受损的机制 饮酒； 2）如果酒精对胎儿生长的影响 骨骼发育是由于大坝无法调节的原因 她的血液ICA水平。 特定目标1将检验的假设 酒精会干扰怀孕大鼠增加的能力 血清PTH的水平和1,25（OH）2d，以响应血液的降低 ICA水平，导致a）缺乏通过 肾脏，b）未能增加肠道Ca的吸收，c） 无法动员骨骼的足够CA。 具体目标2将测试 假设母体血液ICA水平的降低值 胎儿生长和骨骼发育，导致胎儿减少 血液ICA水平，可能a）直接抑制骨形成，或b） 触发胎儿的补偿性反应，例如增加 甲状旁腺激素相关肽（PTHRP）或甲状旁腺的分泌 激素（PTH），可能又可能抑制骨形成。 提议 研究将开始阐明基础的机制 在骨骼质量容易遭受骨骼的两个时期，酒精在骨头上 扰动：怀孕和胎儿发育。 酒精引起的 骨量的扰动可能对 骨质疏松症的发展，这是当今主要的医疗保健问题。