Effect of recombinant human growth hormone on serum Klotho and fibroblast growth factor 23 in children with idiopathic short stature

DONG Han-Han, LI Meng-Meng, SUN Meng, ZHOU Ran, ZHANG Xin-Ying, CHENG Ya-Ying

Chinese Journal of Contemporary Pediatrics ›› 2023, Vol. 25 ›› Issue (11) : 1143-1149.

PDF(577 KB)
PDF(577 KB)
Chinese Journal of Contemporary Pediatrics ›› 2023, Vol. 25 ›› Issue (11) : 1143-1149. DOI: 10.7499/j.issn.1008-8830.2306105
CLINICAL RESEARCH

Effect of recombinant human growth hormone on serum Klotho and fibroblast growth factor 23 in children with idiopathic short stature

  • DONG Han-Han, LI Meng-Meng, SUN Meng, ZHOU Ran, ZHANG Xin-Ying, CHENG Ya-Ying
Author information +
History +

Abstract

Objective To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children. Methods A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes. Results There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05). Conclusions The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.

Key words

Idiopathic short stature / Klotho / Fibroblast growth factor 23 / Insulin-like growth factor-1 / Physical development / Child

Cite this article

Download Citations
DONG Han-Han, LI Meng-Meng, SUN Meng, ZHOU Ran, ZHANG Xin-Ying, CHENG Ya-Ying. Effect of recombinant human growth hormone on serum Klotho and fibroblast growth factor 23 in children with idiopathic short stature[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(11): 1143-1149 https://doi.org/10.7499/j.issn.1008-8830.2306105

References

1 Kumar A, Jain V, Chowdhury MR, et al. Pathogenic/likely pathogenic variants in the SHOX, GHR and IGFALS genes among Indian children with idiopathic short stature[J]. J Pediatr Endocrinol Metab, 2020, 33(1): 79-88. PMID: 31834863. DOI: 10.1515/jpem-2019-0234.
2 Alvarez-Cienfuegos A, Cantero-Nieto L, Garcia-Gomez JA, et al. FGF23-Klotho axis in patients with rheumatoid arthritis[J]. Clin Exp Rheumatol, 2020, 38(1): 50-57. PMID: 31025926.
3 Kurosu H, Ogawa Y, Miyoshi M, et al. Regulation of fibroblast growth factor-23 signaling by Klotho[J]. J Biol Chem, 2006, 281(10): 6120-6123. PMID: 16436388. PMCID: PMC2637204. DOI: 10.1074/jbc.C500457200.
4 Lehtihet M, Stephanou C, B?rjesson A, et al. Studies of IGF-I and klotho protein in relation to anabolic-androgenic steroid and growth hormone administrations[J]. Front Sports Act Living, 2022, 4: 829940. PMID: 35434614. PMCID: PMC9008280. DOI: 10.3389/fspor.2022.829940.
5 Efthymiadou A, Kritikou D, Mantagos S, et al. The effect of GH treatment on serum FGF23 and Klotho in GH-deficient children[J]. Eur J Endocrinol, 2016, 174(4): 473-479. PMID: 26764419. DOI: 10.1530/EJE-15-1018.
6 Guarnotta V, Pizzolanti G, Petrancosta R, et al. Gender-specific soluble α-klotho levels as marker of GH deficiency in children: a case-control study[J]. J Endocrinol Invest, 2022, 45(6): 1247-1254. PMID: 35279809. PMCID: PMC9098545. DOI: 10.1007/s40618-022-01757-y.
7 中华医学会儿科学分会内分泌遗传代谢学组, 《中华儿科杂志》编辑委员会, 梁雁. 基因重组人生长激素儿科临床规范应用的建议[J]. 中华儿科杂志, 2013, 51(6): 426-432. PMID: 24120059. DOI: 10.3760/cma.j.issn.0578-1310.2013.06.007.
8 中华医学会儿科学分会内分泌遗传代谢学组, 《中华儿科杂志》编辑委员会. 中枢性性早熟诊断与治疗共识(2015)[J]. 中华儿科杂志, 2015, 53(6): 412-418. PMID: 26310550. DOI: 10.3760/cma.j.issn.0578-1310.2015.06.004.
9 李辉, 季成叶, 宗心南, 等. 中国0~18岁儿童、青少年身高、体重的标准化生长曲线[J]. 中华儿科杂志, 2009, 47(7): 487-492. PMID: 19951507. DOI: 10.3760/cma.j.issn.0578-1310.2009.07.003.
10 李辉, 季成叶, 宗心南, 等. 中国0~18岁儿童、青少年体块指数的生长曲线[J]. 中华儿科杂志, 2009, 47(7): 493-498. PMID: 19951508. DOI: 10.3760/cma.j.issn.0578-1310.2009.07.004.
11 Cheikhi A, Barchowsky A, Sahu A, et al. Klotho: an elephant in aging research[J]. J Gerontol A Biol Sci Med Sci, 2019, 74(7): 1031-1042. PMID: 30843026. PMCID: PMC7330474. DOI: 10.1093/gerona/glz061.
12 Sanchez-Ni?o MD, Fernandez-Fernandez B, Ortiz A. Klotho, the elusive kidney-derived anti-ageing factor[J]. Clin Kidney J, 2019, 13(2): 125-127. PMID: 32297880. PMCID: PMC7147303. DOI: 10.1093/ckj/sfz125.
13 Zhou H, Pu S, Zhou H, et al. Klotho as potential autophagy regulator and therapeutic target[J]. Front Pharmacol, 2021, 12: 755366. PMID: 34737707. PMCID: PMC8560683. DOI: 10.3389/fphar.2021.755366.
14 Rubinek T, Modan-Moses D. Klotho and the growth hormone/insulin-like growth factor 1 axis: novel insights into complex interactions[J]. Vitam Horm, 2016, 101: 85-118. PMID: 27125739. DOI: 10.1016/bs.vh.2016.02.009.
15 Rubinek T, Shahmoon S, Shabtay-Orbach A, et al. Klotho response to treatment with growth hormone and the role of IGF-I as a mediator[J]. Metabolism, 2016, 65(11): 1597-1604. PMID: 27733247. DOI: 10.1016/j.metabol.2016.08.004.
16 Sen JM. Phenotypes of Klotho[J]. Aging (Albany NY), 2019, 11(14): 4777-4778. PMID: 31326964. PMCID: PMC6682531. DOI: 10.18632/aging.102117.
17 Sze L, Bernays RL, Zwimpfer C, et al. Excessively high soluble Klotho in patients with acromegaly[J]. J Intern Med, 2012, 272(1): 93-97. PMID: 22452701. DOI: 10.1111/j.1365-2796.2012.02542.x.
18 Coopmans EC, El-Sayed N, Frystyk J, et al. Soluble Klotho: a possible predictor of quality of life in acromegaly patients[J]. Endocrine, 2020, 69(1): 165-174. PMID: 32333268. PMCID: PMC7343750. DOI: 10.1007/s12020-020-02306-4.
19 Kuro-O M. The Klotho proteins in health and disease[J]. Nat Rev Nephrol, 2019, 15(1): 27-44. PMID: 30455427. DOI: 10.1038/s41581-018-0078-3.
20 Yamashita T, Yoshioka M, Itoh N. Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain[J]. Biochem Biophys Res Commun, 2000, 277(2): 494-498. PMID: 11032749. DOI: 10.1006/bbrc.2000.3696.
21 ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23[J]. Nat Genet, 2000, 26(3): 345-348. PMID: 11062477. DOI: 10.1038/81664.
22 Shimada T, Mizutani S, Muto T, et al. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia[J]. Proc Natl Acad Sci U S A, 2001, 98(11): 6500-6505. PMID: 11344269. PMCID: PMC33497. DOI: 10.1073/pnas.101545198.
23 Ho BB, Bergwitz C. FGF23 signalling and physiology[J]. J Mol Endocrinol, 2021, 66(2): R23-R32. PMID: 33338030. PMCID: PMC8782161. DOI: 10.1530/JME-20-0178.
24 Agoro R, Ni P, Noonan ML, et al. Osteocytic FGF23 and its kidney function[J]. Front Endocrinol (Lausanne), 2020, 11: 592. PMID: 32982979. PMCID: PMC7485387. DOI: 10.3389/fendo.2020.00592.
25 Takashi Y, Fukumoto S. Phosphate-sensing and regulatory mechanism of FGF23 production[J]. J Endocrinol Invest, 2020, 43(7): 877-883. PMID: 32140858. DOI: 10.1007/s40618-020-01205-9.
26 Meazza C, Elsedfy HH, Khalaf RI, et al. Serum α-Klotho levels are not informative for the evaluation of growth hormone secretion in short children[J]. J Pediatr Endocrinol Metab, 2017, 30(10): 1055-1059. PMID: 28902627. DOI: 10.1515/jpem-2016-0464.
27 Pons-Belda OD, Alonso-álvarez MA, González-Rodríguez JD, et al. Mineral metabolism in children: interrelation between vitamin D and FGF23[J]. Int J Mol Sci, 2023, 24(7): 6661. PMID: 37047636. PMCID: PMC10094813. DOI: 10.3390/ijms24076661.
28 Michigami T, Tachikawa K, Yamazaki M, et al. Growth-related skeletal changes and alterations in phosphate metabolism[J]. Bone, 2022, 161: 116430. PMID: 35577326. DOI: 10.1016/j.bone.2022.116430.
PDF(577 KB)

Accesses

Citation

Detail

Sections
Recommended

/