INHIBITORY EFFECT OF GROWTH-ENHANCING ANTIBODY ON THE INTERACTION BETWEEN GROWTH-HORMONE AND GROWTH-HORMONE BINDING-PROTEIN

A monoclonal antibody (mAb), designated PS-7.6, was generated in mice by immunizing these animals with recombinant porcine growth hormone (p GH). This antibody has been previously shown to enhance the growth-pro moting activity of pGH in an experimental rat model. An effort was mad e in this report to further characterize the immunologic properties of this antibody and its effect on the interaction between pGH and GH bi nding protein (GHBP). This antibody was classified as IgG1 isotype and found to be highly specific to pGH in a competition radioimmunoassay (RIA). It did not recognize several other GHs including those of bovin e, chicken and human origins, nor several growth related factors inclu ding prolactin, insulin, somatostatin and growth hormone releasing fac tor. In Western analysis, PS-7.6 mAb identified not only,the 22.5 kDa recombinant pGH, but also the native pGH in swine pituitary gland. An additional 45 kDa protein was also detected in the gland by the antibo dy, presumably a dimer form of pGH. The association and dissociation r ate constants of the antibody as determined by biospecific interaction analysis (BIA) were 2.43 x 10(4) M-1 s-1 and 1.29 x 10(-3) S-1, respe ctively and its affinity (K(d)) was 4.85 x 10(-8) M. Furthermore, PS-7 .6 mAb prevented pGH from interacting with GHBP in RIA and BIA, indica ting that the antibody epitope closely associated with the pGH binding region for GHBP. Therefore, present findings suggest that a possible mechanism of action of PS-7.6 mAb in enhancing animal growth is to pre vent pGH from being bound to GHBP in circulation, thus making more pGH available to tissue receptors.