Abstract
ObjectiveKlotho 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.DesignProspective 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.ResultsKlotho 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.ConclusionsWe 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.
Highlights
Klotho is a transmembrane protein which can be cleaved, shed and act as a circulating hormone [1]
If validated by additional studies, serum klotho may serve as novel biomarker of organic GH deficiency (GHD)
We aimed to study the association between klotho serum levels, anthropometric measurements, and growth hormone (GH) deficiency (GHD) in children with short stature and growth impairment
Summary
Klotho is a transmembrane protein which can be cleaved, shed and act as a circulating hormone [1]. Klotho-deficient mice (kl/kl) show a shortened life span and multiple disorders resembling human aging [1], while overexpression of klotho increases lifespan [2]. High klotho expression was noted in the distal convoluted tubules in the kidney and the choroid plexus, but klotho is expressed in various endocrine-related tissues including testes, ovaries and the pituitary [1]. Klotho is an essential cofactor for the binding of fibroblast growth factor (FGF) 23 to its cognate receptor, serving as a major regulator of phosphate homeostasis [3,4]. Klotho can enhance the activity of the calcium channels TRPV5/6, and is a potent inhibitor of the activity of the insulin and insulin growth factor (IGF)-1 pathways [2,5,6]
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