A selective decrease of collagen peptide synthesis by dermal polysomes isolated from glucocorticoid-treated newborn rats
Mcnelis, B.; Cutroneo, K.R.
Molecular Pharmacology 14(6): 1167-1175
1978
ISSN/ISBN: 0026-895X PMID: 732814 Document Number: 129096
Polysomes were isolated from the dermis of control newborn rats treated with various pharmacological doses of triamcinolone diacetate and allowed to incorporate radioactive proline into collagen and noncollagen protein in the wheat germ lysate system. Proline incorporation into collagen and noncollagen protein was linearly related to the A260 unit of polysomes added to the lysate system. Proline incorporation into collagen and noncollagen was maximal at 4.6 mM magnesium acetate, 155 mM KCl, 0.017 mM amino acids and 40 .mu.g protein of the wheat germ extract. Proline incorporation into collagen and noncollagen protein was dependent on the presence of amino acids, polysomes, ATP, KCl, Mg and wheat germ extract. Polysomes isolated from glucocorticoid-treated rats incorporated less proline into collagen as compared to proline incorporation into noncollagen protein, indicating a selective decrease of collagen synthesis, although proline incorporation into noncollagen protein was also decreased. This selective decrease of collagen synthesis was dose dependent. Significant inhibition of collagen synthesis was observed at a dose of 2 mg/kg. Maximum inhibition of collagen synthesis was observed at a dose of 12 mg/kg. This selective decrease in collagen synthesis was also dependent on the number of daily injections of glucocorticoid. A selective decrease of collagen synthesis was observed 6 h after a single i.p. injection of 12 mg/kg triamcinolone diacetate. After 3 daily injections of drug at this dose (12 mg/kg), the inhibitory effect on noncollagen and collagen syntheses was doubled. Since amino acids are not rate limiting in this protein sythesizing system in vitro, the glucocorticoid-mediated selective decrease of collagen synthesis in skin does not result from an inhibition of amino acid uptake.