[Suppression of lipotropic action of human somatotropin by protease inhibitors].

The effect of protease inhibitors on the lipotrophic action of the human growth hormone was studied in rabbits in vivo and in vitro. The human growth hormone at a concentration of 25-100 micrograms/ml stimulated lipolysis in isolated rabbit perirenal fat tissue 3-5 fold. An addition of 250 or 500 E Trasylol or 5 mM methylamine to the incubation mixture inhibited the growth hormone lipotrophic effect by 50%. Contrary to these protease inhibitors, the aminopeptidase inhibitor bacitracin did not affect the growth hormone action. Trasylol and methylamine did not diminish either basal or epinephrine-stimulated lipolysis in rabbit fat tissue. In vivo Contrical at the total dose of 5000 E infused 30 min before and 30 min after the growth hormone injection completely abolished the increase of plasma-free fatty acid level induced by the hormone. These data suggest that: 1) the inhibitor suppression of growth hormone lipotrophic action is not due to the inhibitor influence on lipolysis or on hormone action at the cell membrane level but is the result of direct protease inhibiton; 2) the late lipotrophic action of the growth hormone may require preliminary cleavage of the hormone molecule in which serine proteases may be involved.