Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats.
OBJECTIVE
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-del1-4, G120R, K168A, E174A, C182S, del186-191) 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.


CONCLUSIONS
The data indicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildly increased the glomerulosclerosis.
Li
Wei
W
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 200031, China.
Zhu
Li-hua
LH
Wang
En-bi
EB
Ye
Zeng-can
ZC
Lin
Jun
J
Guo
Li-he
LH
Luo
Fei-hong
FH
Liu
Xi-hong
XH
Fang
Xin
X
Shen
Shui-xiang
SX
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003928:Diabetic Nephropathies / Q000209:etiology / Q000473:pathology*; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D016297:Mutagenesis, Site-Directed; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000378:metabolism; D014162:Transfection
D008565:Membrane Proteins; D011986:Receptors, Somatotropin; C405010:delta-hGHR; D019382:Human Growth Hormone