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Molecular Pharmacology, Vol 14, 185-198, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Glucocorticoids Selectively Decrease the Synthesis of Hydroxylated Collagen Peptides

ROBERT A. NEWMAN 1 and KENNETH R. CUTRONEO 1

1 Department of Biochemistry, University of Vermont College of Medicine, Burlington, Vermont 05401

Multiple daily injections of triamcinolone diacetate to newborn rats result in decreased body and skin weight gain, which is related to a specific decrease of collagen polypeptide synthesis. The effects of glucocorticoid administration on protein synthesis of the dermis was determined by measurement of the incorporation of labeled proline. The percentage decrease in collagen synthesis in triamcinolone-treated animals was greater than that of non-collagen protein synthesis at all doses examined, indicating a selective effect of glucocorticoids on collagen synthesis. This selective decrease of collagen synthesis was greatest after multiple injections at higher doses of the steroid. DNA synthesis was also suppressed after multiple injections of steroid. Steroid administration resulted in a decrease in prolyl hydroxylase activity (EC 1.14.11.2) in a dose- and time-dependent manner. Lysyl hydroxylase activity (EC 1.14.11.4) was decreased to the same extent as prolyl hydroxylase activity, while glucose 6-phosphate dehydrogenase activity (EC 1.1.1.49) was unchanged and tyrosine aminotransferase activity (EC 2.6.1.5) was slightly elevated. Collagenase digestion of nascent polypeptide chains released from dermal polysomes demonstrated a selective, dose-dependent decrease in collagen polypeptide synthesis. Furthermore, collagen nascent chain synthesis was decreased to the same extent as hydroxyproline formation, indicating that glucocorticoids do not cause the synthesis and subsequent accumulation of underhydroxylated collagen.

Note:
ACKNOWLEDGMENTS The authors wish to thank Dr. Brian Little for his consultation in evaluating the histological sections, and Dr. Cassius Bordolon for his consultation on preparing the wheat germ lysate system. We also acknowledge the expert technical assistance of Ms. Elizabeth Tuthill, Ms. Gloria Hoff, Mr. Brian McNelis, and Mr. James Evans.

Submitted on July 11, 1977




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