Efthymiadou Alexandra, Kritikou Dimitra, Mantagos Stefanos, Chrysis Dionisios
Division of EndocrinologyDepartment of Pediatrics, Medical School, University of Patras, Rio 26504, Patras, Greece
Division of EndocrinologyDepartment of Pediatrics, Medical School, University of Patras, Rio 26504, Patras, Greece.
Eur J Endocrinol. 2016 Apr;174(4):473-9. doi: 10.1530/EJE-15-1018. Epub 2016 Jan 13.
Normal phosphate homeostasis is essential for normal linear growth. The phosphaturic fibroblast growth factor 23 (FGF23)/Klotho axis is a major regulator of phosphate homeostasis; therefore, an intact FGF23/Klotho axis is important for normal linear growth. On the other hand, GH/IGF1 axis has opposing effects on phosphate homeostasis, but the underline mechanisms remain unclear.
The main objective of this study was to investigate the possible interactions of FGF23 and its co-receptor Klotho, with growth hormone (GH)/IGF1 axis in the regulation of phosphate metabolism in GH-deficient children under GH treatment.
We studied 23 GH-deficient children, before and 3 months after the onset of GH treatment. Anthropometry and assessment of biochemical parameters were performed, as well as measurement of FGF23 (intact FGF23/iFGF23 and C-terminal FGF23/cFGF23) and soluble α-Klotho (sKlotho) levels.
After 3 months on GH treatment, the elevation of serum phosphate and TmPO4/GFR (P<0.0001 and P<0.01 respectively) was accompanied by a significant increase in cFGF23 (P<0.01), iFGF23 (P<0.0001), sKlotho (P<0.0001) and IGF1 (P<0.0001). Serum phosphate and TmPO4/GFR were positively associated with iFGF23 (P<0.01 and P<0.05) and IGF1 (P<0.05 and P<0.05). iFGF23 levels were positively correlated with sKlotho (P<0.001), IGF1 (P<0.0001) and height SDS (P<0.0001), whereas sKlotho was positively associated with IGF1 (P<0.0001) and height SDS (P<0.001).
The increase in serum phosphate, which we found in GH-deficient children under GH treatment, is not associated with suppression but rather than with upregulation of the phosphaturic FGF23/Klotho axis.
正常的磷稳态对于正常的线性生长至关重要。排磷成纤维细胞生长因子23（FGF23）/α-klotho轴是磷稳态的主要调节因子；因此，完整的FGF23/α-klotho轴对于正常的线性生长很重要。另一方面，生长激素（GH）/胰岛素样生长因子1（IGF1）轴对磷稳态有相反的作用，但其潜在机制仍不清楚。
本研究的主要目的是探讨FGF23及其共受体α-klotho与生长激素（GH）/IGF1轴在生长激素缺乏症患儿接受生长激素治疗期间对磷代谢调节中的可能相互作用。
我们研究了23例生长激素缺乏症患儿，在生长激素治疗开始前及治疗3个月后。进行了人体测量和生化参数评估，以及FGF23（完整FGF23/iFGF23和C端FGF23/cFGF23）和可溶性α-klotho（sKlotho）水平的测定。
生长激素治疗3个月后，血清磷和TmPO4/GFR升高（分别为P<0.0001和P<0.01），同时cFGF23（P<0.01）、iFGF23（P<0.0001）、sKlotho（P<0.0001）和IGF1（P<0.0001）显著增加。血清磷和TmPO4/GFR与iFGF23（P<0.01和P<0.05）以及IGF1（P<0.05和P<0.05）呈正相关。iFGF23水平与sKlotho（P<0.001）、IGF1（P<0.0001）和身高标准差评分（P<0.0001）呈正相关，而sKlotho与IGF1（P<0.0001）和身高标准差评分（P<0.001）呈正相关。
我们发现生长激素缺乏症患儿在接受生长激素治疗期间血清磷升高，这与排磷FGF23/α-klotho轴的抑制无关，而是与该轴的上调有关。
