THE EFFECT OF GH THERAPY ON THE IMMUNOREACTIVE FORMS AND DISTRIBUTIONOF IGFBP-3, IGF-I, THE ACID-LABILE SUBUNIT, AND GROWTH-RATE IN GH-DEFICIENT CHILDREN

We have previously shown that the major correlates of growth following growth hormone (GH) therapy in growth hormone-deficient (GHD)children are changes in circulating insulin-like growth factor-1 (IGF-1) and I CF binding protein-3 (IGFBP-3), suggesting a synergistic interaction b etween IGF-1 and ICFBP-3 (1). The first aim of this project was to exa mine the molecular forms of IGFBP-3 and the acid-labile subunit (ALS), and to assess the changes in these molecular forms during CH administ ration to GHD children. Plasma samples from prepubertal GHD patients, prior to therapy and during the first year of GH treatment, were subje cted to Western ligand and immunoblot analysis. Densitometric analysis of Western ligand blotting (WLB) showed a 76% increase in IGFBP-3 (p = 0.02), but a 56% decrease in 36-kDa IGFBP-2 (p = 0.03) during GH the rapy. Western immunoblot (WlB) analysis of IGFBP-3 revealed the presen ce of intact (40- to 45-kDa doublet) as well as a proteolyzed (28-kDa) form of IGFBP-3 in the serum of GHD and healthy children. Both immuno reactive forms of IGFBP-3 increased by 64% during GH therapy (intact p = 0.003; proteolyzed p = 0.0001). WlB analysis of the ALS showed an 8 4- to 86-kDa doublet, which increased by 41% with GH therapy (p = 0.01 ). The response to CH therapy, as measured by the height velocity stan dard deviation score (SDS) adjusted for bone age, correlated with the percent change in total IGFBP-3 (r = 0.772, p = 0.002 by WlB), intact IGFBP-3 (r = 0.845, p = 0.0005 by WLB; r = 0.541, p = 0.05 by WlB), an d proteolyzed IGFBP-3 (r = 0.703, p = 0.007), as well as with the perc ent change in ALS (r = 0.813, p = 0.014).