Insulin-like growth factor binding proteins (IGFBPs) in acromegaly

Hypersecretion of growth hormone (GH) is the principal feature of acromegaly and is accompanied by an excess of IGF-I production which mediates some of the actions of GH. The activity of IGF-I is modulated by a number of specific binding proteins (IGFBPs) which form complexes with IGF-I in the circulation. In this study, the technique of Western Ligand Blotting followed by 2-dimensional radioactive scanning was employed to investigate the correlations between relative levels of the IGFBPs and the main factors implicated in their regulation: IGF-I, GH and insulin, in a group of acromegalics with varying disease activity. The two glycosylated forms of IGFBP-3 correlated with increased levels of IGF-I (40.5 kD, r = 0.468, p <or = 0.01 and 36.5 kD, r = 0.809, p <or = 0.001), but did not relate to mean GH levels. Quantification of IGFBP-2 on the ligand blot showed an association with RIA levels of IGFBP-1 (r = 0.35, p <or = 0.05). IGFBP-1 RIA levels did not relate to the radioactivity in the assumed IGFBP-1 region of the ligand blot. This may be explained by fragments of IGFBP-3 running in this region and could account for the correlation seen between radioactivity in the 29 kD band with both forms of IGFBP-3 as well as with IGFBP-4. IGFBP-3 levels were normal in biochemically cured acromegalics with normal GH levels, although fasting insulin levels remained higher than normal (mean 16 +/- 4 vs normal 7.4 +/- 0.4 mU/L).(ABSTRACT TRUNCATED AT 250 WORDS)