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 HYP X, circulating insulin-like growth factor I (IGF-I) levels were dimini shed, 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 I-12 5-IGF-I to, isolated glomerular membranes and proximal tubule basolate ral membranes (BLM) was increased in HYPX rats. Affinity labeling of m embranes with I-125-IGF-I followed by electrophoresis on 6% polyacryla mide gels demonstrated two bands, one of similar to 140 kDa and anothe r of > 200 kDa. The lower-molecular-mass protein, which has been ident ified as the a-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 immun ostaining as IGF binding protein 5 (IGFBP-5), not IGFBP-1 or IGFBP-2. Affinity labeling documented an upregulation of this protein in both m embranes after HYPX. Ligand blotting demonstrated a 31-kDa protein in HYPX cortical but not normal cortical or medullary cytosol that was im muno-stained with IGFBP-5 antibodies. RNA prepared from normal kidney cortical tissue demonstrated a 6.0-kb IGFBP-5 transcript, which was in creased at day 14 after HYPX. Adaptations in the kidney after HYPX inc lude an upregulation of the IGF-I receptor as well as IGFBP-5. The pre sence of IGFBP-5 in cytosol of renal tissue after HYPX suggests the po ssibility of ligand secretion when circulating levels of IGF-I are dim inished. IGFBP-5 may serve as an extravascular reservoir for IGF-I tha t limits degradation and facilitates growth factor interaction with th e receptor.