Increased proportion of circulating non-22-kilodalton growth hormone isoforms in short children: A possible mechanism for growth failure

被引:40
作者
Boguszewski, CL
Jansson, C
Boguszewski, MCS
Rosberg, S
Carlsson, B
AlbertssonWikland, K
Carlsson, LMS
机构
[1] GOTHENBURG UNIV, RES CTR ENDOCRINOL & METAB, DEPT INTERNAL MED, S-41345 GOTHENBURG, SWEDEN
[2] GOTHENBURG UNIV, INT PEDIAT GROWTH RES CTR, DEPT PEDIAT, S-41345 GOTHENBURG, SWEDEN
关键词
D O I
10.1210/jc.82.9.2944
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Current knowledge about the interaction between GH and its receptor suggests that the molecular heterogeneity of circulating GH may have important implications for growth. The aim of this study was to investigate the proportion of circulating non-22-kDa GH isoforms in prepubertal children with short stature (height less than -2 so score) of different etiologies. We have also evaluated the relationships among the ratio of non-22-kDa GH isoforms, auxology, and spontaneous GH secretion. The study groups consisted of 17 girls with Turner's syndrome (TS), aged 3-13 yr; 25 children born small for gestational age (SGA) without postnatal catch-up growth, aged 3-13 yr; and 24 children with idiopathic short stature (ISS), aged 4-15 yr. The results were compared with those from 23 prepubertal healthy children of normal stature (height +/- 2 so score), aged 4-13 yr. Serum non-22-kDa GH levels, expressed as a percentage of the total GH concentration, were determined by the 22-kDa GH exclusion assay, which is based on immunomagnetic extraction of monomeric and dimeric 22-kDa GH from serum and quantitation of non-22-kDa GH using a polyclonal antibody-based GH assay. All samples were selected from spontaneous GH peaks in 24-h GH profiles. The median proportion of non-22-kDa GH isoforms was increased in children born SGA (9.8%; P = 0.05) and girls with TS (9.9%; P = 0.01), but not in the group of children with ISS (8.9%), compared with that in normal children (8.1%). Individually, increased proportions of non-22-kDa GH isoforms, with values more than 2 so above the mean for the normal group, were observed in 5 girls with TS, 5 children born SGA, and 4 children with ISS. In children horn SGA, the proportion of non-22-kDa GH isoforms was directly correlated with different estimates of spontaneous GK secretion [mean 24-h GH concentration (r = 0.41; P = 0.04), area under the curve over baseline (r = 0.41; P = 0.04), and GH peak area (r = 0.61; P = 0.003)], whereas it was inversely correlated with height sn score (r = -0.42; P = 0.04). In conclusion, an increased proportion of circulating non-22-kDa GH isoforms was observed at spontaneous GH peaks in some non-GH-deficient short children. Our results suggest that the ratio of non-22-kDa GH isoforms in the circulation may have important implications for normal and abnormal growth.
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页码:2944 / 2949
页数:6
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