INSULIN-LIKE GROWTH FACTOR-I RECEPTOR AND BINDING-PROTEINS IN RAT-KIDNEY AFTER NEPHRON LOSS

Insulin-like growth factor (IGF)-binding proteins and the IGF-I recept or in rat kidney were studied to gain perspective on their potential r oles in the control of renal cell mass. Thirty days after nephrectomy (UNx), membranous whole-kidney binding of IGF-I averaged 9.5 +/- 1.0 p mol/kidney, whereas binding to sham-operated controls (SNx) averaged 6 .3 +/- 0.8 pmol/kidney (N = 6; P < 0.01). Scatchard analysis of IGF-I binding per milligram of protein to glomerular membranes or proximal t ubule basolateral membranes (BLM) at Day 30 did not reveal significanc e differences in B(max) or K(D) between SNx and UNx; however, protein per glomerulus increased from 361 +/-33 ng/glomerulus in SNx animals t o 826 +/- 123 ng/glomerulus in UNx rats (N = 6; P < 0.002). Histomorph ometrics documented an increase in proximal tubule circumference per c ell and an increase in the basolateral/basement membrane ratio. IGF-I affinity labeling studies demonstrated three proteins in both glomerul ar membranes and proximal tubule BLM; molecular weight approximately 1 40,000 d, the alpha subunit of the IGF-I receptor, a protein >200,000 d, and a protein approximately 31,000 d that was immunostained with IG F-binding protein-5 antibodies. Differences in expression between SNx and UNx were not observed at Day 30 in either glomeruli or BLM. These studies suggest that cytosolic hypertrophy of proximal nephron structu res is accompanied by membrane hypertrophy with o fixed density of IGF -I receptor and IGF-binding protein-5.