MONOCLONAL-ANTIBODIES TO BOVINE GROWTH-HORMONE POTENTIATE HORMONAL ACTIVITY IN-VIVO BY ENHANCING GROWTH-HORMONE BINDING TO HEPATIC SOMATOGENIC RECEPTORS

Administration of CH complexed with monoclonal antibodies (MABs) poten tiates the in vivo actions of the hormone. In particular, growth and s erum IGF-I concentrations of GH-treated hypophysectomized rats are inc reased by concomittant injection of anti-GH MABs. Among 37 anti-bovine GH (bGH) MABs, we selected one MAB with the most potentiating effects to investigate the mechanisms responsible for this phenomenon. Hypoph ysectomized rats were killed 18 h after a single s.c. injection of bGH (100 mu g/rat), alone or complexed with increasing doses of MAB (4, 4 0, 400 mu g/rat; MAB:bGH molar ratio : 0.005, 0.05, 0.5). IGF-I was me asured by radioimmunoassay in acid-extracted sera and livers, whereas liver IGF-I mRNA was quantified by Northern blot hybridization. The in vivo occupancy of liver somatogenic (GH) receptors was derived from t he determinations of total and free I-125-labelled bGH binding to live r homogenates treated with 4 mol MgCl2/l or water. Injection of MAB-bG H complexes enhanced body weight gain and raised serum IGF-I, liver IG F-I and liver IGF-I mRNA more than bGH alone (1.6-, 6-, 10- and 7-fold increases at the highest dose of MAB, compared with bGH alone; P<0.00 1). These potentiating effects of the MAB were dose-dependent and sign ificant potentiation of the growth response was already observed with the lowest dose of MAB. In vivo occupancy of liver GH receptors was ma rkedly higher 18 h after injection of MAB-bGH complexes than after bGH alone, and this effect was also dose-dependent (receptor occupancy of 28%, 37% and 83% after 4, 40 and 400 mu g of MAB respectively compare d with 6% after bGH alone; P<0.05, 0.05 and 0.001 respectively). In co ntrast, the in vitro binding of I-125-labelled bGH to liver homogenate s was decreased in the presence of high doses of MAB. We conclude that low amounts of MABs complexed with bGH potentiate the stimulation by the hormone of liver IGF-I synthesis and secretion in a dose-dependent manner. These effects are mediated, at least in part, through changes in hormone-receptor interaction in vivo, leading to enhanced and/or p rolonged binding of bGH to its somatogenic receptors.