%0 Journal Article
%T Growth hormone (GH)©\transgenic insulin©\like growth factor 1 (IGF1)©\deficient mice allow dissociation of excess GH and IGF1 effects on glomerular and tubular growth
%A Andreas Blutke
%A Eckhard Wolf
%A Marlon R. Schneider
%A R¨¹diger Wanke
%J Archive of "Physiological Reports".
%D 2016
%R 10.14814/phy2.12709
%X Growth hormone (GH)©\transgenic mice with permanently elevated systemic levels of GH and insulin©\like growth factor 1 (IGF1) reproducibly develop renal and glomerular hypertrophy and subsequent progressive glomerulosclerosis, finally leading to terminal renal failure. To dissociate IGF1©\dependent and ©\independent effects of GH excess on renal growth and lesion development in vivo, the kidneys of 75 days old IGF1©\deficient (I £¿/£¿) and of IGF1©\deficient GH©\transgenic mice (I £¿/£¿ /G), as well as of GH©\transgenic (G) and nontransgenic wild©\type control mice (I +/+) were examined by quantitative stereological and functional analyses. Both G and I £¿/£¿ /G mice developed glomerular hypertrophy, hyperplasia of glomerular mesangial and endothelial cells, podocyte hypertrophy and foot process effacement, albuminuria, and glomerulosclerosis. However, I £¿/£¿ /G mice exhibited less severe glomerular alterations, as compared to G mice. Compared to I +/+ mice, G mice exhibited renal hypertrophy with a significant increase in the number without a change in the size of proximal tubular epithelial (PTE) cells. In contrast, I £¿/£¿ /G mice did not display significant PTE cell hyperplasia, as compared to I £¿/£¿ mice. These findings indicate that GH excess stimulates glomerular growth and induces lesions progressing to glomerulosclerosis in the absence of IGF1. In contrast, IGF1 represents an important mediator of GH©\dependent proximal tubular growth in GH©\transgenic mice
%K Glomerulosclerosis
%K kidney
%K quantitative stereology
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823598/