A proposed mechanism of action of a growth hormone-specific monoclonal antibody in the enhancement of hormonal activity.
The potentiation of the biological activity of recombinant porcine growth hormone (pGH) by immunologic manipulation was investigated. An anti-pGH monoclonal antibody, designated PS-7.6, was generated and its effect on pGH was evaluated in hypophysectomized (hypox) rats. As expected, administration with pGH for 5 consecutive days promoted these animals to grow. The effect was further augmented when pGH was given together with PS-7.6 antibody and the enhancing ability of the antibody lasted beyond the treatment period. The growth profile of rats receiving antibody alone did not differ from that of untreated controls, indicating that PS-7.6 antibody by itself was not a growth stimulant. The possible mechanism of action of the antibody was investigated by analyzing blood and tissue samples of animals following injection with 125I-labeled pGH either in its free form or complexed with PS-7.6 antibody. As compared to the pGH levels in animals receiving free pGH, approximately a half pGH was released into circulation from the injection sites when it was given in a complex form. Furthermore, 2-4-fold increases in pGH deposition were also found in various tissues of animals treated with pGH-antibody complexes over that of respective tissues of animals receiving free pGH. Therefore, the present findings suggest that PS-7.6 antibody is capable of augmenting the somatogenesis of pGH and the effect is, at least in part, explainable by its ability in altering the pharmacokinetics and biodistribution of pGH in animals.
Wang
B S
BS
Laboratory of Immunoendocrinology, American Cyanamid Company, Princeton, NJ 08543.
Lumanglas
A L
AL
Szewczyk
E
E
McWilliams
W
W
Loullis
C C
CC
Hart
I C
IC
D000818:Animals; D000911:Antibodies, Monoclonal; D004357:Drug Synergism; D005260:Female; D006128:Growth / Q000187:drug effects*; D013006:Growth Hormone / Q000276:immunology* / Q000493:pharmacokinetics / Q000494:pharmacology; D007016:Hypophysectomy; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D015430:Weight Gain / Q000187:drug effects
D000911:Antibodies, Monoclonal; D013006:Growth Hormone