Increased glomerular size occurs in the presence of normal maturation following unilateral nephrectomy in humans and animals and in disease states such as diabetes mellitus. The glomeruli are morphologically and functionally normal following nephrectomy in rats unless the remaining renal mass is severely reduced, in which case progressive glomerulosclerosis ensues. The hormonal regulation of compensatory hypertrophy is not fully understood, however total kidney IGF-I mRNA levels are increased following unilateral nephrectomy. This suggests a role for this hormone in hypertrophy of the adult kidney as well as in normal development. There are abnormalities in the circulating levels of GH in some diseases associated with increases in glomerular extracellular matrix and cell number such as diabetes mellitus. The availability of transgenic mouse strains expressing elevated levels of IGF-I, GH, and GHRF provides and opportunity to study the renal effects of chronic hormone exposure. We have observed that mice containing an MT-I IGF-I fusion gene develop large glomeruli which are normal in appearance, whereas those transgenic for either growth hormone or growth hormone releasing factor have large glomeruli which are hypercellular, whereas progressive glomerulosclerosis develops later.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
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Country
United States
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