Somatomedin production by rat liver in organ culture

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Abstract
Inhibitors of cartilage sulfation were released by the rat liver in organ culture. They cause a decrease in [35S]sulfate uptake by embryonic chick cartilage and, when added to a constant amount of serum, counteract serum somatomedin (SM) activity. Both of these effects are dose-dependent. Their antagonistic action, investigated in the presence of increasing serum concentrations, 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 .mu.g/ml) increased the sulfation-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 G75 showed that at pH 7.9, inhibitors eluted in the same fractions as [125I]SM-A bound to its carrier (apparent MW .apprx. 45,000) and that 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 as to whether the cartilage sulfation inhibitor might not be the same molecule as the SM-carrier protein released by the liver.