Human Growth Hormone Receptor Antagonist On Glomerular Sclerosis In Stz-induced Diabetic Rats

Two human Growth Hormone(hGH) mutants, hGHA1(Cys-hGH-del 1-4, G120R, K168A, E174A, del 186-191), hGHA2(H21A, G120R, E174A), were expressed in E.coli. The IC50s, at which 50 percent of binding of 125I-hGH to rabbit liver membrane GH receptor was inhibited, were 65±10ng/250ul for hGHA1, 27±5.6mg/250ul for hGHA2. The results of OGTT indicated hGH(1mg/kg body weight·day for 3 days, s.c.)or hGHA1(5mg/kg body weight·day for 3 days, s.c.)was diabetogenic, while hGHA2(5mg/kg body weight·day for 3 days, s.c.) was not. Treatment with hGHA2 at 4mg/kg body weight·day(s.c.), for 12 weeks inhibited the glomerulosclerosis in STZ-induced diabetic SD rats, while treatment with hGH at 1 unit/kg body weight·day (s.c.) or hGHA1 at 4mg/kg body weight·day (s.c.) for 12 weeks led to more severe glomerulosclerosis in STZ-induced diabetic SD rats compared with that in the STZ-induced diabetic SD rats treated with 0.3ml saline per day for 12 weeks.