Proteolytic processing of human growth hormone (GH) by rat tissues in vitro: Influence of sex and age

Although a wealth of evidence exists indicating that proteolytic cleavage c an enhance the biological activity of the growth hormone (GH) molecule, the mechanisms responsible for the generation of GH fragments are not complete ly understood. In the present work we investigated the ability of different rat tissues to cleave 22 kDa GH, as well as the influence of sex and age, the two major physiological regulators of GH secretion on this process. Our results show that tissue homogenates obtained from rat liver, skeletal mus cle or adipose tissue (three well-documented target organs for the hormone) are able to cleave 22K-GH, while the hormone is resistant to cleavage by r at brain homogenates. This process is rather selective for 22K-GH, since th e 20 kDa GH variant exhibits stability to degradation by all tissue homogen ates investigated. Moreover, only a minor fraction of 22 kDa GH is cleaved under our experimental conditions, suggesting that GH microheterogeneity wi thin the 22 kDa range may also determine hormone susceptibility. Finally, w e also found that 22K-GH processing shows important age-related changes (th e greatest intensity observed in 4-day-old pups), while no gender-related d ifferences exist in any of the tissues investigated. (C) 2000, Editrice Kur tis.