GLUCOCORTICOID INHIBITION OF GAGS BIOSYNTHESIS: POSSIBLE SITE OF ACTION

Abstract

Glucocorticoid hormones inhibit the biosynthesis of glycosaminoglycans (GAGS) which are essential for normal skeletal growth. Previous studies have shown that these hormones alter both somatomedin, which stimulates GAGS biosynthesis, and the cartilage cell directly. We have further studied the effect of cortisol on GAGS biosynthesis in embryonic chick cartilage. When cortisol was administered to 9 day old embryos 24 hours prior to injecting radioactive precursors, 35SO4 uptake into GAGS was decreased 70%. 14C-proline into OH-proline 14%, 14C-serine into protein 15% and 3H-thymidine into DNA 17%, suggesting cortisol specifically inhibited GAGS biosynthesis without comparable inhibition of DNA or protein biosynthesis. Assays of the glycosyltransferases responsible for the formation of the protein-polysaccharide linkage region in cartilage from cortisol treated embryos showed xylosyltransferase activity decreased by 50% in both long and short term incubations, while the activities of other glycosyltransferases were unchanged. Addition of exogenous xylose acceptor stimulated the activity several fold. In vitro addition of cortisol to the enzyme assays was without effect. These data suggest the site of action of cortisol is to decrease the endogenous acceptor protein in growing cartilage or the activity of the enzyme, xylosyl transferase.