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Am J Physiol Renal Physiol 266: F147-F154, 1994;
0363-6127/94 $5.00
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AJP - Renal Physiology, Vol 266, Issue 1 147-F154, Copyright © 1994 by American Physiological Society

ARTICLES

IGF binding protein 5 and IGF-I receptor regulation in hypophysectomized rat kidneys

M. K. Hise, N. M. Mantzouris, J. S. Lahn, M. S. Sheikh, Z. M. Shao and J. A. Fontana
Department of Internal Medicine, University of Maryland Medical School, Baltimore 21201.

This study examines growth-regulating adaptations made by the proximal nephron in response to hypophysectomy (HYPX). Fourteen days after HYPX, circulating insulin-like growth factor I (IGF-I) levels were diminished, averaging 97 +/- 7 compared with 650 +/- 69 ng/ml in controls (n = 5, P < 0.001). Similar data were observed at day 7. Binding of 125I-IGF-I to isolated glomerular membranes and proximal tubule basolateral membranes (BLM) was increased in HYPX rats. Affinity labeling of membranes with 125I-IGF-I followed by electrophoresis on 6% polyacrylamide gels demonstrated two bands, one of approximately 140 kDa and another of > 200 kDa. The lower-molecular-mass protein, which has been identified as the alpha-subunit of the IGF-I receptor, and the higher-molecular-mass species were both upregulated by HYPX. Ligand blotting with IGF-I demonstrated a 31-kDa protein in both membranes, identified by immunostaining as IGF binding protein 5 (IGFBP-5), not IGFBP-1 or IGFBP-2. Affinity labeling documented an upregulation of this protein in both membranes after HYPX. Ligand blotting demonstrated a 31-kDa protein in HYPX cortical but not normal cortical or medullary cytosol that was immunostained with IGFBP-5 antibodies. RNA prepared from normal kidney cortical tissue demonstrated a 6.0-kb IGFBP-5 transcript, which was increased at day 14 after HYPX. Adaptations in the kidney after HYPX include an upregulation of the IGF-I receptor as well as IGFBP-5.(ABSTRACT TRUNCATED AT 250 WORDS)


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[Abstract] [Full Text] [PDF]


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