1,25-DIHYDROXYVITAMIN D RECEPTOR/FUNCTION IN NEW TARGETS

新靶标中的 1,25-二羟基维生素 D 受体/功能

• 批准号: 3230389
• 负责人: MARIAN R WALTERS
• 金额: $ 9.68万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3230389
• 关键词: 1,25 dihydroxycholecalciferol; Sertoli cells; binding proteins; calcium metabolism; calmodulin; dietary calcium; dietary trace element; heart contraction; histochemistry /cytochemistry; homeostasis; immunochemistry; laboratory rat; muscle cells; muscle pharmacology; myocardium; nutrition related tag; organelles; phosphorus; radiotracer; receptor; testis; tissue /cell culture

The overall goal of this project is to elucidate the function(s) of 1,25-dihydroxyvitamin D3(1,25(OH)2D3), or the lack thereof, in new putative target tissues by addressing the hypothesis that 1,25(OH)2D3, exerts specific and important effects therein via previously described receptors. Thus, 1,25(OH)2D3 function will be rigorously evaluated by a series of physiological and biochemical criteria in the model systems rat heart and testis. The first phases of these studies are focused on testing the hypothesis that 1,25(OH)2D3 plays a role in intracellular calcium homeostasis. However, because of the fallacy in limiting such studies to any one area of possible functions, the hypothesis that 1,25(OH)2D3 affects these systems through alternate mechanisms must be tested in the future. Whether there is a correlation between vitamin D status or 1,25(OH)2D3 receptor and physiological function will be tested by evaluating the effects of vitamin D status in normocalcemic rats on the contractile properties of heart muscles and on testicular function and examining whether 1,25(OH)2D3 receptor levels in putative new target tissues correlate with physiological status of the vitamin D endocrine system. Effects of 1,25(OH)2D3 status and receptors on intracellular calcium homeostasis in heart and Sertoli cells will be evaluated by studying the hormonal effects on uptake of 45Ca into intact cultured heart myocytes and Sertoli cells. Effects of 1,25(OH)2D3 on selected mechanisms/subcellular organelles will be evaluated by determining 45Ca uptake in heart myocytes and Sertoli cells in the absence and presence of pharmacological probes. Additional studies will extend studies of the effects of 1,25(OH)2D3 status/receptors on calcium binding proteins detected by 45CA binding to proteins transblotted to nitrocellulose membranes, on proteins modulated by calmodulin by the 125-I-calmodulin gel overlay technique, and by immunocytochemical localization of calcium binding proteins that demonstrate vitamin D regulation. These interrelated studies of 1,25(OH)2D3 function and receptors in putative new targets will add much to our understanding of the vitamin D endocrine system and will provide a basis for future assessments of 1,25(OH)2D3 function in both normal and diseased individuals.

该项目的总体目标是阐明功能 1,25-二羟基维生素D3（1,25（oh）2d3），或缺乏的1,25-二羟基维生素 通过解决以下假设： 1,25（OH）2d3，通过其中发挥特定而重要的效果 先前描述的受体。 因此，1,25（OH）2d3功能将 通过一系列生理和 模型系统大鼠心脏和睾丸的生化标准。 这些研究的第一阶段的重点是测试 假设1,25（OH）2d3在细胞内钙中起作用 稳态。 但是，由于限制了这种谬论 对任何可能功能的任何一个领域的研究，这是 1,25（OH）2d3必须通过替代机制影响这些系统 将来要测试。 是否之间存在相关性 维生素D状态或1,25（OH）2d3受体和生理功能 将通过评估维生素D状态在 心脏肌肉收缩特性的正常大鼠 以及睾丸功能并检查1,25（OH）2d3是否 推定的新靶组织中的受体水平与 维生素D内分泌系统的生理状态。 效果 1,25（OH）2d3状态和受体在细胞内钙上 心脏和Sertoli细胞中的稳态将通过 研究荷尔蒙对45CA摄取完整的影响 培养的心肌细胞和Sertoli细胞。 1,25（OH）2d3的效果 在选定的机制/亚细胞器中将通过 确定心脏肌细胞和Sertoli细胞的45CA摄取 药理学探针的不存在和存在。 其他研究 将扩展对1,25（OH）2d3状态/受体的影响的研究 在45CA与蛋白质结合检测的钙结合蛋白上 传输到硝酸纤维素膜，在调制的蛋白质上 通过125-i-钙调蛋白凝胶覆盖技术的钙调蛋白，并通过 钙结合蛋白的免疫细胞化学定位 证明维生素D调节。 这些相互关联的研究 假定的新目标中的1,25（OH）2d3功能和受体将增加 我们对维生素D内分泌系统和 将为将来评估1,25（OH）2d3功能提供基础 在正常和患病的人中。