Department of Nephrology, Herlev Hospital, University of Copenhagen, 2730, Copenhagen, Denmark.
Department of Nephrology, Rigshospitalet Copenhagen, University of Copenhagen, Copenhagen, Denmark.
Calcif Tissue Int. 2018 Jan;102(1):85-92. doi: 10.1007/s00223-017-0333-9. Epub 2017 Oct 23.
The calcium and phosphate homeostasis is regulated by a complex interplay between parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and calcitriol. Experimental studies have demonstrated an inhibitory effect of FG23 on PTH production and secretion; the physiological role of this regulation is however not well understood. Surprisingly, in uremia, concomitantly elevated FGF23 and PTH levels are observed. The parathyroid gland rapidly loses its responsiveness to extracellular calcium in vitro and a functional parathyroid cell line has currently not been established. Therefore, the aim of the present investigation was to study the impact of FGF23 on the Ca/PTH relationship in vivo under conditions of normocalcemia and hypocalcemia. Wistar rats were allocated to treatment with intravenous recombinant FGF23 and inhibition of the FGF receptor in the setting of normocalcemia and acute hypocalcemia. We demonstrated that FGF23 rapidly inhibited PTH secretion and that this effect was completely blocked by inhibition of the FGF receptor. Furthermore, inhibition of the FGF receptor by itself significantly increased PTH levels, indicating that FGF23 has a suppressive tonus on the parathyroid gland's PTH secretion. In acute hypocalcemia, there was no effect of either recombinant FGF23 or FGF receptor inhibition on the physiological response to the low ionized calcium levels. In conclusion, FGF23 has an inhibitory tonus on PTH secretion in normocalcemia and signals through the FGF receptor. In acute hypocalcemia, when increased PTH secretion is needed to restore the calcium homeostasis, this inhibitory effect of FGF23 is abolished.
钙和磷酸盐的动态平衡是由甲状旁腺激素 (PTH)、成纤维细胞生长因子 23 (FGF23) 和 1,25-二羟维生素 D3 (calcitriol) 之间的复杂相互作用调节的。实验研究表明 FGF23 对 PTH 的产生和分泌有抑制作用；然而，这种调节的生理作用尚未得到很好的理解。令人惊讶的是，在尿毒症中，同时观察到 FGF23 和 PTH 水平升高。体外甲状旁腺对细胞外钙的反应迅速丧失，并且目前尚未建立功能性甲状旁腺细胞系。因此，本研究旨在研究在正常钙血症和低钙血症条件下 FGF23 对 Ca/PTH 关系的影响。Wistar 大鼠被分配接受静脉内重组 FGF23 治疗和在正常钙血症和急性低钙血症中抑制 FGF 受体。我们证明 FGF23 可迅速抑制 PTH 的分泌，而这种作用被 FGF 受体的抑制完全阻断。此外，FGF 受体的抑制本身显著增加了 PTH 水平，表明 FGF23 对甲状旁腺的 PTH 分泌具有抑制张力。在急性低钙血症中，重组 FGF23 或 FGF 受体抑制对低离子钙水平的生理反应均无影响。总之，FGF23 在正常钙血症中对 PTH 的分泌具有抑制张力，并通过 FGF 受体传递信号。在急性低钙血症中，当需要增加 PTH 分泌以恢复钙稳态时，FGF23 的这种抑制作用被消除。
