Kobayashi Keisuke, Imanishi Yasuo, Miyauchi Akimitsu, Onoda Naoyoshi, Kawata Takehisa, Tahara Hideki, Goto Hitoshi, Miki Takami, Ishimura Eiji, Sugimoto Toshitsugu, Ishikawa Tetsuro, Inaba Masaaki, Nishizawa Yoshiki
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Eur J Endocrinol. 2006 Jan;154(1):93-9. doi: 10.1530/eje.1.02053.
While the importance of fibroblast growth factor (FGF)-23 is established in phosphate-wasting disorders, little is known about the mechanisms regulating its circulating level. To investigate the role of parathyroid hormone (PTH) and calcium in FGF-23 metabolism, we examined plasma FGF-23 levels in patients with primary hyperparathyroidism (PHPT).
Fifty patients with PHPT and 52 controls were employed in this study. Plasma was obtained from 18 PHPT patients who underwent parathyroidectomy (PTX) on the first postoperative morning without vitamin D administration. Time-course samples were also obtained from 5 of 18 PTX patients without vitamin D analogs or calcium administration. The expression of Fgf23 on resected parathyroid glands was analyzed by reverse transcription (RT)-PCR and immunohistochemistry.
FGF-23 was significantly elevated in PHPT patients compared with controls. FGF-23 levels were significantly correlated positively with serum corrected calcium and intact PTH levels, and negatively with creatinine clearance and inorganic phosphate, among which creatinine clearance and corrected calcium were independently associated factors. In 18 PTX patients, postoperative FGF-23 levels were significantly decreased compared with preoperative levels. Corrected-calcium levels were significantly decreased 1 h after PTX, and this was followed by a reduction in plasma FGF-23 levels in time-course study. In addition, postoperative FGF-23 levels in 18 PTX patients were significantly correlated with corrected calcium, consistent with a role of serum calcium as one of the major regulators of FGF-23. The absence of Fgf23 expression in parathyroid glands indicated that the parathyroid glands were not major sources of circulating FGF-23.
Serum calcium may regulate circulating FGF-23 levels in PHPT.
虽然成纤维细胞生长因子（FGF）-23在磷消耗性疾病中的重要性已得到确立，但关于调节其循环水平的机制却知之甚少。为了研究甲状旁腺激素（PTH）和钙在FGF-23代谢中的作用，我们检测了原发性甲状旁腺功能亢进症（PHPT）患者的血浆FGF-23水平。
本研究纳入了50例PHPT患者和52例对照。从18例在术后第一个早晨未补充维生素D的情况下接受甲状旁腺切除术（PTX）的PHPT患者中获取血浆。还从18例PTX患者中的5例未补充维生素D类似物或钙的患者中获取了时间进程样本。通过逆转录（RT）-PCR和免疫组织化学分析切除的甲状旁腺中Fgf23的表达。
与对照组相比，PHPT患者的FGF-23显著升高。FGF-23水平与血清校正钙和完整PTH水平呈显著正相关，与肌酐清除率和无机磷呈负相关，其中肌酐清除率和校正钙是独立相关因素。在18例PTX患者中，术后FGF-23水平较术前显著降低。在时间进程研究中，PTX后1小时校正钙水平显著降低，随后血浆FGF-23水平降低。此外，18例PTX患者术后FGF-23水平与校正钙显著相关，这表明血清钙是FGF-23的主要调节因子之一。甲状旁腺中缺乏Fgf23表达表明甲状旁腺不是循环FGF-23的主要来源。
血清钙可能调节PHPT患者的循环FGF-23水平。
