Bergwitz Clemens, Jüppner Harald
Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Endocr Dev. 2009;16:133-56. doi: 10.1159/000223693. Epub 2009 Jun 3.
Phosphate is absorbed from the diet in the gut, stored as hydroxyapatite in the skeleton, and excreted with the urine. The balance between these compartments determines the circulating phosphate concentration. Fibroblast growth factor 23 (FGF23) has recently been discovered and is part of a previously unrecognised hormonal bone-kidney axis. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome, and dentin matrix protein 1 regulate the expression of FGF23 in osteocytes, which then is O-glycosylated by UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl-transferase 3 and secreted into the circulation. FGF23 binds with high affinity to fibroblast growth factor receptor 1c in the presence of its co-receptor Klotho. It inhibits, either directly or indirectly, reabsorption of phosphate and the synthesis of 1,25-dihydroxy-vitamin-D by the renal proximal tubule and the secretion of parathyroid hormone by the parathyroid glands. Acquired or inborn errors affecting this newly discovered hormonal system can lead to abnormal phosphate homeostasis and/or tissue mineralisation. This chapter will provide an update on the current knowledge of the pathophysiology, the clinical presentation, diagnostic evaluation and therapy of the disorders of phosphate homeostasis and tissue mineralisation.
磷酸盐在肠道中从饮食中被吸收，以羟基磷灰石的形式储存在骨骼中，并随尿液排出。这些部分之间的平衡决定了循环中的磷酸盐浓度。成纤维细胞生长因子23（FGF23）最近被发现，是以前未被认识的激素骨-肾轴的一部分。与X染色体上的内肽酶具有同源性的磷酸盐调节基因和牙本质基质蛋白1调节骨细胞中FGF23的表达，然后该蛋白被UDP-N-乙酰-α-D-半乳糖胺：多肽N-乙酰半乳糖胺基转移酶3进行O-糖基化并分泌到循环中。在其共受体Klotho存在的情况下，FGF23与成纤维细胞生长因子受体1c高亲和力结合。它直接或间接抑制肾近端小管对磷酸盐的重吸收和1,25-二羟基维生素D的合成，以及甲状旁腺对甲状旁腺激素的分泌。影响这个新发现的激素系统的获得性或先天性缺陷可导致异常的磷酸盐稳态和/或组织矿化。本章将提供关于磷酸盐稳态和组织矿化紊乱的病理生理学、临床表现、诊断评估和治疗的当前知识的最新情况。
