Somatomedin production by rat liver in organ culture

Abstract

Abstract. Inhibitors of cartilage sulphation have been found to be released by the rat liver in organ culture. They cause a decrease in [35S]sulphate uptake by embryonic chick cartilage and, when added to a constant amount of serum, counteract the somatomedin (SM) activity of the serum. Both of these effects are dose-dependent. Their antagonistic action, investigated in the presence of increasing concentrations of serum, appeared to resemble non-competitive inhibition which would suggest different sites of action for SM and inhibitors. Incubation of the liver explants with cortisol (0.01—1 μg/ml) increased the sulphation-inhibiting activity of the culture medium and the effect was dose-dependent. Simultaneous addition of cycloheximide suppressed the inhibition. Gel filtration of the culture medium on Sephadex G 75 showed that: a) at pH 7.9, inhibitors eluted in the same fractions as [125I]SM-A bound to its carrier (apparent molecular weight ∼45 000); b) at pH 2.4, inhibitors still eluted as large molecules, but SM activity appeared in the same fractions as the dissociated [125I]SM-A. The question arises whether the cartilage sulphation inhibitor might not be the same molecule as the SM-carrier protein released by the liver.