Reversible dimerization of 20 kilodalton human growth hormone (hGH)

A noncovalent dimer of the 22 kilodalton human growth hormone (22 K-hGH) is known to have diminished somatogenic activity compared with monomeric 22 K -hGH. In the present study, we examined the biological activity and physico chemical behaviour of a noncovalent dimer of the 20 kilodalton human growth hormone (20 K-hGH), an isoform of 22 K-hGH. Analysis of the equilibrium be tween monomeric and associated forms revealed that the associated 20 K-hGH was present in the dimeric form in aqueous solution. The kinetics of dimeri zation in rat plasma followed the theory of dissociation-association equili brium, and more than 99% of 20 K-hGH molecules existed as a monomer in the equilibrium state at the physiological hGH concentration. Analysis of the p harmacokinetics showed that the ratio of the administrated dimer in rat cir culation decreased from 43% to less than 4% in 2 h. A preparation of noncov alent dimeric 20 K-hGH had essentially the same degree of biological potenc y as that of a monomer in both in vitro and in vivo bioassays. In conclusio n, dimerization of 20 K-hGH is reversible both in vitro and in vivo and a n oncovalent dimer can function as a pharmaceutically active component of a 2 0 K-hGH preparation, in contrast to a 22 K-hGH preparation. (C) 2000 Harcou rt Publishers Ltd.