Enhancement of bovine growth hormone activity in vivo by monoclonal antibodies.
Monoclonal antibodies (MAbs) prepared against ovine growth hormone (oGH) and recognizing several distinct or related specificities on bovine growth hormone (bGH), have been shown to strikingly enhance the growth promoting properties of the hormone in vivo as determined by 35SO2-4 incorporation in cartilage. The phenomenon is dependent on both hormone and antibody dose and is saturable in the presence of excess antibody. Competition binding analysis between pairs of antibodies has shown that they define distinct antigenic regions on bGH of which one is represented by four MAbs. The most potent growth enhancement was associated with a group of three MAbs (OA11, OA12 and OA13) binding to topographically closely related sites. Another MAb (OA14) with a specificity similar to OA11 and OA13 as defined by competition assay failed to enhance bGH activity. Two antibodies binding to a further two sites (OA15 and OA16) demonstrated modest growth enhancement activity when in complex with bGH, whereas the binding of another antibody (OA17) did not significantly affect hormonal activity. Univalent antibody fragments (Fab) derived from MAb OA11 were equi-potent to the bivalent form of the antibody in the enhancement of bGH activity. Determination of the effects of the different MAbs on the binding of 125I-bGH to liver microsome receptors revealed substantial increase in specific binding (3.5-fold) and is associated with some growth enhancing MAbs. However, not all growth enhancing MAbs increased receptor binding and in the case of one, OA16, clear cut inhibition of receptor binding was observed. Tentative conclusions have been drawn on the possible underlying mechanisms of the MAb mediated enhancement phenomenon.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D002358:Cartilage, Articular / Q000378:metabolism; D002417:Cattle; D000939:Epitopes / Q000032:analysis; D006128:Growth; D013006:Growth Hormone / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011986:Receptors, Somatotropin / Q000378:metabolism; D012756:Sheep; D013454:Sulfoxides / Q000378:metabolism; D013552:Swine
D000911:Antibodies, Monoclonal; D000939:Epitopes; D011986:Receptors, Somatotropin; D013454:Sulfoxides; D013006:Growth Hormone