Yan Xu1, Ming-Chao Liu2, Pei Wang1, Bei Xu1, Xin-Qin Liu2, Zhi-Ping Zhang1, Li-Fen Ren1, Qing Qin1, Yue-Yun Ma1, Wen-Jing Luo2, Xiao-Ke Hao1. 1. Department of Clinical Laboratories, Xijing Hospital, Fourth Military Medical University Xi'an 710032, China. 2. Department of Occupational & Environmental Health and The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University Xi'an 710032, China.
Abstract
UNLABELLED: This study aimed to investigate correlation between serum insulin-like growth factor-1 (IGF-1) and blood lead level in short stature children with growth hormone deficiency (GHD), and IGF-1 signal molecules were investigated in lead exposed rats. Our findings may provide evidence for clarifying pathogenesis of lead induced short stature in children. METHODS: 880 short stature children were recruited from clinics and divided into GHD group and idiopathic short stature (ISS) group according to the GH peak in growth hormone stimulation test. The height, body weight, serum IGF-1 level and blood lead level were determined. A rat model of lead poisoning was used to establish and western blot assay was employed to detect the phosphorylation of signaling molecules (MAPK and PI3K/Akt) related to IGF-1 signaling pathway. RESULTS: In GHD group, the height, body weight and serum IGF-1 level were significantly lower, but the blood lead level was significantly higher than those in ISS group (P<0.05). Western blot assay confirmed that the protein expression of phosphorylated ERK1/2, JNK, p38, Akt473 and Akt308 increased significantly (P<0.01) in lead exposure rats. CONCLUSION: Our study suggesting that reduction in IGF-1 in children with GHD is associated with blood lead level. Lead exposure may induce expression of phosphorylated MAPK and Akt signaling molecules. The activation of these molecules may influence binding of IGF-1 and tyrosine kinase receptor IGFIR to regulate cell growth via the MAPK and Akt signaling pathways, which then interfere with growth-promoting effect of IGF-1 in short children.
UNLABELLED: This study aimed to investigate correlation between serum insulin-like growth factor-1 (IGF-1) and blood lead level in short stature children with growth hormone deficiency (GHD), and IGF-1 signal molecules were investigated in lead exposed rats. Our findings may provide evidence for clarifying pathogenesis of lead induced short stature in children. METHODS: 880 short stature children were recruited from clinics and divided into GHD group and idiopathic short stature (ISS) group according to the GH peak in growth hormone stimulation test. The height, body weight, serum IGF-1 level and blood lead level were determined. A rat model of lead poisoning was used to establish and western blot assay was employed to detect the phosphorylation of signaling molecules (MAPK and PI3K/Akt) related to IGF-1 signaling pathway. RESULTS: In GHD group, the height, body weight and serum IGF-1 level were significantly lower, but the blood lead level was significantly higher than those in ISS group (P<0.05). Western blot assay confirmed that the protein expression of phosphorylated ERK1/2, JNK, p38, Akt473 and Akt308 increased significantly (P<0.01) in lead exposure rats. CONCLUSION: Our study suggesting that reduction in IGF-1 in children with GHD is associated with blood lead level. Lead exposure may induce expression of phosphorylated MAPK and Akt signaling molecules. The activation of these molecules may influence binding of IGF-1 and tyrosine kinase receptor IGFIR to regulate cell growth via the MAPK and Akt signaling pathways, which then interfere with growth-promoting effect of IGF-1 in short children.
Entities:
Keywords:
Growth hormone deficiency; insulin-like growth factor I; lead exposure animal model; short stature; signaling pathway
Authors: V Gasco; G Corneli; G Beccuti; F Prodam; S Rovere; J Bellone; S Grottoli; G Aimaretti; E Ghigo Journal: Eur J Endocrinol Date: 2008-09-19 Impact factor: 6.664
Authors: Apoina Kartini; Hertanto W Subagio; Suharyo Hadisaputro; Martha I Kartasurya; Suhartono Suhartono; Budiyono Budiyono Journal: Int J Occup Environ Med Date: 2019-01