Glucocorticoids selectively decrease the synthesis of hydroxylated collagen peptides
Newman, R.A.; Cutroneo, K.R.
Molecular Pharmacology 14(1): 185-198
1978
ISSN/ISBN: 0026-895X PMID: 24169 Document Number: 124814
Multiple daily triamcinolone diacetate injections to newborn rats decreased body and skin weight gain, which is related to a specific decrease of collagen polypeptide synthesis. Effects of glucocorticoid administration on dermal protein synthesis was determined by measurement of labeled proline incorporation. 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 steroid doses. DNA synthesis was suppressed after multiple steroid injections. Steroid administration decreased in prolyl hydroxylase activity (EC 1.14.11.2) in a dose- and time-dependent manner. Lysyl hydroxylase activity (EC 1.14.11.4) 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. Collagen nascent chain synthesis decreased to the same extent as hydroxyproline formation, indicating that glucocorticoids did not cause synthesis and subsequent accumulation of underhydroxylated collagen.