IDENTIFICATION OF TRANSFORMED ALPHA(2)-MACROGLOBULIN AS A GROWTH HORMONE-BINDING PROTEIN IN HUMAN BLOOD

WE, have found that the human GH forms complexes with the purified pro teinase inhibitor, alpha(2)-macroglobulin. This inhibitor occurs in tw o different forms in human blood, known as native and transformed alph a(2)-macroglobulin. It could be clearly demonstrated by chromatography and electrophoresis combined with autoradiography that the GH binds s pecifically to the transformed inhibitor, but not to the native protei n. The binding was characterized as being mainly noncovalent to specif ic binding sites present only in the transformed inhibitor molecule. B inding analysis using antibody precipitation technique revealed two di fferent classes of binding sites with dissociation constants of 0.49 /- 0.12 and 61 +/- 8 mu mol/L for high and low affinity binding sites, respectively. Distribution analysis of I-125-labeled GH in whole plas ma suggested that the hormone is bound to different proteins: 1) to th e high affinity GH-binding protein, and 2) to the low affinity GH-bind ing protein identified as transformed alpha(2)-macroglobulin.