Correlation between serum IGF-1 and blood lead level in short stature children with growth hormone deficiency

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Objective To investigate the correlation between serum insulin-like growth factor-1 (IGF-1) and blood lead levels in short stature children with growth hormone deficiency (GHD), and study the changes of IGF-1 signal molecules in lead exposed rats, providing evidence for clarifying the pathogenesis of lead induced short stature in children. Methods Totally 800 short stature children were recruited in the clinical case-control study during June 2011 to March 2013 and were divided into GHD group or idiopathic short stature (ISS) group according to the their GH peak in growth hormone stimulation test. The serum IGF-1 levels and blood lead levels were determined. A lead poisoning model in rats was established and Western blot assay was employed to detect the phosphorylation of signaling molecules (MAPK and PI3K/AKT) related to IGF-1 signaling pathway. The average independent samples T-test and non-parametric Mann-Whitney test were used for statistical analysis. Results GHD children accounted for 41.14% (362 cases) of the 880 short stature cases. Serum IGF-1 levels in GHD group were (20.02±11.24) μmol/L in female and (20.74±13.39) μmol/L in male, which were significantly lower than the ISS Group with (46.58±27.00) μmol/L in female and (35.91±20.05) μmol/L in male (t=10.45, 9.98 respectively, both P<0.01.) However, the blood lead levels of GHD group (0.49±0.18 μmol/L in female, 0.46±0.18 μmol/L) in male were significantly higher than those in ISS group [(0.32±0.11) μmol/L in female, (0.34±0.13 μmol/L in male]. All had a statistically significant difference (t=-10.91 and -9.056, both P<0.01). Atomic absorption spectrophotometry showed the blood lead level in rats treated with lead containing water for 6 weeks significantly increased when compared with control group. Western blot assay confirmed that the protein expression of phosphorylated ERK1/2, JNK, p38, AKT473 and AKT308 increased significantly than the total enzyme in lead exposure rats. In AKT308/t-AKT group, the protein expression levels in the control group and 300 ppm group were 1.320±0.071 and 2.960±0.552(F=19.360, P<0.01). In AKT473/t-AKT group, the protein expression levels in the control group and 300 ppm group were 0.311±0.038 and 1.018±0.282, respectively(F=16.101, P<0.01) .In p-ERK/t-ERK group, the protein expression levels in the control group and 300 ppm group were 1.173±0.109 and 6.438±0.748(F=72.054, P<0.01). In p-JNK/t-JNK group, the protein expression levels in the control group and 300 ppm group were 1.249±0.129 and 4.869±0.907(F=35.528, P<0.01). In p-P38/t-P38 group, the protein expression levels in the control group and 300 ppm group were 0.083±0.022 and 0.500±0.038(F=57.29, P<0.01). Conclusions The study suggests that reduction in IGF-1 in children with GHD is associated with an increased blood lead level. Lead possibly affects the IGF-1-mediated growth-promoting effect of GH by increasing the phosphorylation of molecules involved in MAPK, AKT and other IGF-1-related signaling pathways, eventually leading to the occurrence of child GHD and short stature. (Chin J Lab Med, 2015, 38: 238-242) Key words: Dwarfism, pituitary; Lead; Lead poisoning; Growth hormone; Insulin-like growth factor I; Disease models, animal