Wolf Ido, Shahmoon Shiri, Ben Ami Michal, Levy-Shraga Yael, Mazor-Aronovitch Kineret, Pinhas-Hamiel Orit, Yeshayahu Yonatan, Hemi Rina, Kanety Hannah, Rubinek Tami, Modan-Moses Dalit
Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Pediatric Endocrinology and Diabetes Unit, The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
PLoS One. 2014 Sep 8;9(9):e107174. doi: 10.1371/journal.pone.0107174. eCollection 2014.
Klotho is an aging-modulating protein expressed mainly in the kidneys and choroid plexus, which can also be shed, released into the circulation and act as a hormone. Klotho deficient mice are smaller compared to their wild-type counterparts and their somatotropes show marked atrophy and reduced number of secretory granules. Recent data also indicated an association between klotho levels and growth hormone (GH) levels in acromegaly. We aimed to study the association between klotho levels and GH deficiency (GHD) in children with growth impairment.
Prospective study comprising 99 children and adolescents (aged 9.0 ± 3.7 years, 49 male) undergoing GH stimulation tests for short stature (height-SDS = -2.1 ± 0.6). Klotho serum levels were measured using an α-klotho ELISA kit.
Klotho levels were significantly lower (p<0.001) among children with organic GHD (n = 11, 727 ± 273 pg/ml) compared to both GH sufficient participants (n = 59, 1497 ± 754 pg/ml) and those with idiopathic GHD (n = 29, 1645 ± 778 pg/ml). The difference between GHS children and children with idiopathic GHD was not significant. Klotho levels positively correlated with IGF-1- standard deviation scores (SDS) (R = 0.45, p<0.001), but were not associated with gender, pubertal status, age or anthropometric measurements.
We have shown, for the first time, an association between low serum klotho levels and organic GHD. If validated by additional studies, serum klotho may serve as novel biomarker of organic GHD.
α-klotho是一种主要在肾脏和脉络丛中表达的衰老调节蛋白,它也可以脱落,释放到循环中并作为一种激素发挥作用。与野生型小鼠相比,α-klotho基因敲除小鼠体型更小,其生长激素细胞显示出明显萎缩,分泌颗粒数量减少。最近的数据还表明肢端肥大症患者的α-klotho水平与生长激素(GH)水平之间存在关联。我们旨在研究生长发育障碍儿童的α-klotho水平与生长激素缺乏症(GHD)之间的关联。
一项前瞻性研究,纳入99名儿童和青少年(年龄9.0±3.7岁,49名男性),因身材矮小(身高标准差评分[height-SDS]=-2.1±0.6)接受生长激素刺激试验。使用α-klotho ELISA试剂盒测量血清α-klotho水平。
与生长激素充足的参与者(n = 59,1497±754 pg/ml)和特发性生长激素缺乏症患者(n = 29,1645±778 pg/ml)相比,器质性生长激素缺乏症儿童(n = 11,727±273 pg/ml)的α-klotho水平显著降低(p<0.001)。生长激素充足儿童与特发性生长激素缺乏症儿童之间的差异不显著。α-klotho水平与胰岛素样生长因子-1标准差评分(SDS)呈正相关(R = 0.45,p<0.001),但与性别、青春期状态、年龄或人体测量指标无关。
我们首次证明血清α-klotho水平低与器质性生长激素缺乏症之间存在关联。如果经其他研究验证,血清α-klotho可能作为器质性生长激素缺乏症的新型生物标志物。