The effect of selective growth hormone defect in the progression of glomerulosclerosis.
The role of endogenous growth hormone (GH) in the progression of glomerulosclerosis was examined in a new mutant strain of Sprague-Dawley (SD) rats with a selective GH gene defect. Fifteen spontaneous dwarf [GH(-)] rats and 10 SD rats underwent subtotal nephrectomy (Nx) or sham operation. Twelve weeks after Nx, the mean arterial pressure, glomerular filtration rate, urinary protein excretion rate, glomerular size, and frequency of glomerulosclerosis were examined. Marked elevation in mean arterial pressure was seen in both SD/Nx and GH(-)/Nx rats. In both strains, the glomerular filtration rate at 12 weeks after Nx was approximately 50% to 60% of that seen in the respective Sham-operated rat groups. The urinary protein excretion rate increased significantly only in the SD/Nx rats. The glomerular size, expressed as the ratio of glomerular volume to body weight, increased by 200% in the SD/Nx rats compared with the SD/Sham rats, in marked contrast to the 70% increase in the GH(-)/Nx rats compared with the GH(-) rats. The frequency of glomerulosclerosis in the GH(-)/Nx rats (1.0 +/- 0.5%) was significantly lower than that in the SD/Nx rats (16.7 +/- 2.8%). The frequency of glomerulosclerosis correlated with glomerular hypertrophy in both the SD and GH(-) rats (r = 0.88 and 0.67, respectively). These results show that the progression of glomerular sclerosis was markedly attenuated in the GH-defective rats. This attenuation of structural injury was correlated with a marked decrease in glomerular hypertrophy. These studies indicate that this specific growth regulatory peptide of endogenous origin plays an important determining role in the progression of glomerulosclerosis.
Yoshida
H
H
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Mitarai
T
T
Kitamura
M
M
Suzuki
T
T
Ishikawa
H
H
Fogo
A
A
Sakai
O
O
D000704:Analysis of Variance; D000818:Animals; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*; D013006:Growth Hormone / Q000502:physiology*; D007678:Kidney Glomerulus / Q000473:pathology* / Q000503:physiopathology*; D009392:Nephrectomy; D009929:Organ Size; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley
D013006:Growth Hormone