Anti-inflammatory Steroids and Collagen Metabolism: Glucocorticoid-Mediated Alterations of Prolyl Hydroxylase Activity and Collagen Synthesis

Several daily injections of triamcinolone diacetate to newborn rats resulted in a decrease of prolyl hydroxylase activity in skin. After labeling of glucocorticoid-treated animals with radioactive proline, hydroxyproline formation was decreased to a greater extent than total proline incorporation, indicating a specific effect on collagen biosynthesis. In contrast, 12 hr after a single injection of steroid, when enzyme activity was only slightly decreased, the depressed level of hydroxyproline formation was almost totally accounted for by the decrease of total proline incorporation. The specific activity of the proline precursor pool was unchanged in animals receiving one or three injections of drug as compared to controls. After 3 days of steroid treatment the amounts of deoxyribonucleic acid, protein, and proteinaceous hydroxyproline per skin were decreased to the same extent as skin weight. Our data indicate that the general antianabolic effect of glucocorticoids on protein synthesis is succeeded by a specific effect on collagen synthesis. The decrease of prolyl hydroxylase which is realized only after multiple injections of glucocorticoids is associated with this specific effect on hydroxyproline formation. These data suggest that the decrease of prolyl hydroxylase following treatment with glucocorticoids is involved in the molecular mechanism of action of this class of drugs on collagen biosynthesis.