Similarity of somatomedin inhibitor in sera from starved, hypophysectomized, and diabetic rats: distinction from a heat-stable inhibitor of rat cartilage metabolism.

The inhibitory effects of sera from starved, hypophysectomized, and alloxan-diabetic rats on basal and somatomedin-stimulated sulfate incorporation into cartilage from hypophysectomized rats were compared. The somatomedin inhibitory activity in serum from diabetic rats behaved like that in serum from starved rats on heating at 60 C. Both were labile in the native sera (pH 8.3-8.4), but activity was conserved to a large extent by lowering the pH to 7.4 and diluting the sera before heating. In all of these sera the peak of the somatomedin inhibitory activity was eluted from a column of Sephacryl S-200 at pH 7.4 just after albumin, and lesser amounts were eluted with albumin and higher molecular weight components. Activity of this type was undetectable in fractions prepared from sera that had been heated at 60 C. These results indicate the similarity of this inhibitor in starved, hypophysectomized, and diabetic rat sera. Certain fractions of both starved and diabetic rat sera, which were eluted from a column of Sephacryl S-200 beyond the total bed volume, contained heat-stable inhibitory activity. In contrast to the effects of the heat-labile inhibitor, these fractions only inhibited basal sulfate incorporation into hypophysectomized rat cartilage under the assay conditions employed. This heat-stable inhibitor was not detected in fractions of hypophysectomized rat serum, and inhibitory concentrations of corticosterone were present in fractions of starved and diabetic rat sera containing the material. The findings suggest that the heat-stable inhibitor is corticosterone.