Modulation of the effectiveness of growth hormone with a monoclonal antibody.
A monoclonal antibody (mAb), designated PS-11.2, was generated by immunizing mice with recombinant porcine growth hormone (pGH). This antibody recognized GHs of porcine, bovine (bGH) and chicken (cGH) origins, but not human GH, ovine prolactin, somatostatin S-14, and GH-releasing factor (1-29)-NH2. Western analysis indicated that PS-11.2 predominantly identified not only the 22.5-kD protein but also its 45-kD dimer. It also recognized the 4.5- and 10-kD fragments of pGH resulting from trypsin digestion. The binding kinetics of PS-11.2 to pGH was determined by the biospecific interaction analysis in a real-time mode. The association and dissociation rate constants were estimated as 1.4 x 10(5) M-1 s-1 and 2.2 x 10(-4) s-1, respectively, thus producing an overall affinity of Kd = 1.6 x 10(-9) M. It partially inhibited the interaction of pGH and GH-binding protein in a competitive radioimmunoassay, suggesting that the pGH epitope recognized by PS-11.2 was closely related to the region responsible for engaging with GH receptors. Growth-deficient hypophysectomized rats were used for functional evaluation and shown to grow in response to the treatment of pGH. This effect was further augmented when pGH was administered together with PS-11.2, although antibody itself did not promote the growth of these animals. The antibody-mediated effect continued beyond the 5-day treatment period, indicating its long-lasting effect. Similar enhancement by PS-11.2 was also observed with bGH and cGH in this rat model.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
R J
RJ
Laboratory of Immunoendocrinology, American Cyanamid Company, Princeton, N.J. 08543-04000, USA.
Lumanglas
A A
AA
Wang
B S
BS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D001667:Binding, Competitive; D015374:Biosensing Techniques; D002417:Cattle; D002645:Chickens; D005260:Female; D013006:Growth Hormone / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000276:immunology; D012756:Sheep; D013045:Species Specificity; D013552:Swine; D015430:Weight Gain / Q000187:drug effects
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D013006:Growth Hormone