Promotion of animal growth with a monoclonal antibody specific to growth hormone receptor

Antibodies to receptors have been shown to act as ligands capable of activating a number of metabolic cellular processes upon engaging with the receptors. However, the demonstration of the biological effect of antireceptor antibodies in intact animals was not very successful. Therefore, a monoclonal antibody (mAb), designated 2C3, was raised by immunizing mice with rat growth hormone binding protein (GHBP). 2C3 was highly active in competing with radioactive porcine growth hormone (pGH) for the binding to GH receptors in a radioimmunoassay, suggesting that the epitope recognized by 2C3 was at or very close to the receptor binding site for GH. The binding affinity of 2C3 to GH receptor was very similar to that of pGH because the competition curve produced by the antibody and cold pGH were identical. 2C3 promoted the growth of GH-deficient rats and the effect was abolished when the antibody was injected into rats together with GHBP which was not active by itself. A control mAb that recognized GH receptor at a region distal from the binding site for GH failed to induce the growth of these rats. Therefore, findings from the present study indicate that 2C3 mAb is capable of engaging with GH receptor at the binding site for GH and triggering a growth response in rats. This antibody may also prove useful as a biological active ligand for better understanding the interaction between the GH and its receptor.