,Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-ind

• 作 者: Wei LI Li-hua ZHU En-bi WANG Zeng-can YE Jun LIN Li-he GUO Fei-hong LUO Xi-hong LIU Xin FANG Shui-xian SHEN
• 机 构: Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Science,Chinese Academ
• 出 处: 中国药理学报（英文版）
• 发表日期: 2004年4期
• 关键词: growth hormone diabetic nephropathies mutation diabetes mellitus

AIM: To explore the feasibility of human growth hormone (hGH) receptor antagonist in the treatment of end-stage diabetic renal complications. METHODS: Two hGH mutants, hGHA1 (Cys-hGH-dell-4, G120R, K168A, E174A,C182S, de1186-191) and hGHA2 (hGH-H21A, G120R, E174A) were expressed in E coli. The IC50 (Mean±SD)values for the mutants for inhibiting 125I-hGH binding to rabbit growth hormone receptor were (65±10) ng for hGHA1, (27±5.6) ng for hGHA2, and (10±0.6) ng for wild type hGH, respectively. RESULTS: After treatment for 12 weeks, the renal histology analysis showed that treatment with hGHA2 at 4 mg/kg body weight daily markedly suppressed glomerulosclerosis in streptozotocin-induced diabetic Sprague-Dawley (SD) rats; hGHA1 at the same dosage slightly increased the renal damage compared with saline; while wild type hGH at 1 U/kg body weight daily severely worsened the glomerulo-sclerosis in diabetic SD rats. CONCLUSION: The data indicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildly increased the glomerulosclerosis.