Inhibition of collagen biosynthesis and increases in low molecular weight IGF-I binding proteins in the skin of fasted rats

Insulin-like growth factor-I (IGF-I) is an important stimulator of collagen biosynthesis and prolidase activity in connective tissue cells. The distur bances in skin collagen metabolism (reflected by significant decrease in sk in collagen content, collagen biosynthesis and prolidase activity) in faste d rats were accompanied by decrease in serum IGF-I level. Fasted rat serum was found to contain about 58% of IGF-I (101.6 +/- 15.4 ng/ml) as compared to control rat serum (175.7 +/- 19.8 ng/ml), while the skin of control and fasted rats contained similar concentrations of IGF-I (about 77 ng/g tissue ). The insulin-like growth factor binding proteins (ICFBPs) of sera and tis sue extracts (known to regulate IGF-I activity) were analysed by ligand blo tting. In the serum of control rats one IGFBP band of about 46 kDa (corresp onding to the acid-dissociated IGFBP-3) was detected. In the serum of faste d rats the 46 kDa IGFBP was not observed, however, an other IGFBP of about 30 kDa (corresponding to low molecular weight IGFBPs, e.g. IGFBP-1 or IGFBP -2) was found. The intensity of IGF-I binding to the 30 kDa IGFBP was much higher than that of ICFBP-3, found in control rat serum. Control and fasted rat skin contained similar IGFBPs, however their IGF-I binding abilities w ere much lower, compared to their serum counterparts. It was found that 46 kDa and 30 kDa proteins, observed in ligand blotting represent IGFBP-3 and IGFBP-1 or IGFBP-2, respectively as demonstrated by western immunoblot anal ysis. An increase in IGF-binding to 30 kDa IGFBP-1 and/or IGFBP-2 (known as an inhibitors of IGF-dependent functions) in the skin of fasted rats may e xplain the mechanism of reduced collagen biosynthesis and deposition in tis sues during fasting. (C) 2000 Elsevier Science Inc. All rights reserved.