Dietary and hormonal regulation of FGF-23 in humans

人类 FGF-23 的饮食和激素调节

• 批准号: 7147855
• 负责人: SHERRI-ANN M BURNETT-BOWIE
• 金额: $ 14.55万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7147855
• 关键词: 1,25 dihydroxycholecalciferol; blood chemistry; circadian rhythms; clinical research; dietary calcium; dietary control; fibroblast growth factor; hormone regulation /control mechanism; human subject; nutrition related tag; parathyroid hormones; patient oriented research; phosphates; phosphorus metabolism; vitamin D deficiency

DESCRIPTION (provided by applicant): Phosphate (PO4) is essential for bone mineralization, muscle function, signal transduction and the creation and utilization of energy. Abnormal PO4 handling occurs in forms of hypophosphatemic rickets, and in chronic renal failure with resultant parathyroid hyperplasia and osteodystrophy. Data from three PO4 wasting disorders (X-linked hypophosphatemia, autosomal dominant hypophosphatemic rickets, and tumor induced osteomalacia) demonstrate that fibroblast growth factor 23 (FGF-23) is a novel phosphaturic hormone that is responsible for severe phosphate wasting in these rare patients. The overarching goal of this proposal is to describe the role of FGF-23 in normal P04 physiology and factors that regulate FGF-23. In each of these protocols, we will measure FGF-23, blood and urinary PO4, and other hormones known to affect PO4, like parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D. In Specific Aim 1, 20 healthy subjects will consume a research diet, and undergo 24 hour blood and urine frequent sampling to assess the diurnal variation in FGF-23. We hypothesize that the diurnal variation in FGF-23, as measured by cosinor analysis, will parallel that of blood PO4 and the renal clearance of PO4, and differ from that of PTH. In Specific Aim 2, 100 healthy vitamin D-deficient subjects will be randomly assigned to calcium 500 mg BID or calcium 500 mg BID plus vitamin D 50,000 units Q WK for 12 weeks to determine whether vitamin D increases FGF-23 levels after controlling for changes in blood PO4 and PTH. To determine the effects of PTH suppression on FGF-23, in Specific Aim 3, 44 healthy subjects will be randomly assigned to either placebo or a calcimimetic, Cinacalcet 30 mg QD (which lowers PTH levels), and concurrently phosphate loaded to determine whether P04 loading increases FGF-23 levels independently of PTH. Finally, to determine effect of PTH stimulation on FGF-23, in Specific Aim 4, we will measure FGF-23 in 58 healthy men who were infused with human PTH(1-34) at a dose of 0.55 U/kg/hr to determine whether PTH has a direct effect on FGF-23 in humans. To summarize, FGF-23 is responsible for phosphate wasting in several rare disorders and appears to play a vital role in normal phosphate physiology. The studies in this proposal will advance our understanding of the hormonal regulation of FGF-23 in humans and may help in the development of novel treatments for patients with hypo- or hyperphosphatemic disorders.

描述（由申请人提供）：