IGF binding protein 5 and IGF-I receptor regulation in hypophysectomized rat kidneys.
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)
Hise
M K
MK
Department of Internal Medicine, University of Maryland Medical School, Baltimore 21201.
Mantzouris
N M
NM
Lahn
J S
JS
Sheikh
M S
MS
Shao
Z M
ZM
Fontana
J A
JA
D000222:Adaptation, Physiological; D000818:Animals; D001345:Autoradiography; D002352:Carrier Proteins / Q000378:metabolism*; D007016:Hypophysectomy; D018975:Insulin-Like Growth Factor Binding Protein 5; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism
D002352:Carrier Proteins; D018975:Insulin-Like Growth Factor Binding Protein 5; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I