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.

酒精对成人和发育中的骨骼有有害影响 动物。 我们实验室之前的工作表明，长期饮酒 大鼠怀孕期间会降低出生体重并导致胎儿发育迟缓 骨骼发育。 此外，我们还表明，酒精 食用对孕妇本身的骨骼有不利影响。 重要的是，我们的研究表明酒精会损害大脑的能力 怀孕母鼠和胎儿调节其钙代谢。 胎儿的生命和 怀孕期间骨骼容易受到酒精的影响 对胎儿骨骼生长发育产生不良影响 以及大坝需要增加的钙来支持其矿化。 在本提案中，我们将扩大对孕妇的研究 进一步研究酒精对女性和胎儿的影响 Ca 调节和骨骼。 我们的具体目标是确定：1​​) 妊娠大鼠钙调节受损的机制 饮酒； 2) 酒精是否对胎儿生长有影响 骨骼发育是由于大坝无法调节的结果 她的血液 iCa 水平。 具体目标 1 将检验以下假设： 酒精会干扰怀孕大鼠的生长能力 血液中 PTH 和 1,25(OH)2D 的血清水平下降 iCa 水平，导致 a) Ca 重吸收缺乏增加 肾，b) 未能增加肠道钙吸收，以及 c) 无法从骨骼中调动足够的钙。 具体目标2将测试 母体血液 iCa 水平降低会导致胎儿迟缓的假设 胎儿生长和骨骼发育会导致胎儿的减少 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），这可能反过来抑制骨形成。 拟议的 研究将开始阐明影响的机制 骨量易受影响的两个时期内酒精对骨骼的影响 干扰：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，这是当今的一个主要卫生保健问题。