Glucocorticoids decrease the synthesis of type I procollagen mRNAs.
Glucocorticoids selectively decrease procollagen synthesis in animal and human skin fibroblasts. beta-Actin content and beta-actin mRNA are not affected by glucocorticoid treatment of chick skin fibroblasts. The inhibitory effect of glucocorticoids on procollagen synthesis is associated with a decrease in total cellular type I procollagen mRNAs in chick skin fibroblasts. These effects of dexamethasone are receptor mediated as determined by pretreatment with the glucocorticoid antagonists progesterone and RU-486 and with the agonist beta-dihydrocortisol. Dexamethasone has a small but significant inhibitory effect on cell growth of chick skin fibroblasts. The ability of this corticosteroid to decrease the steady-state levels of type I procollagen mRNAs in nuclei, cytoplasm, and polysomes varies. The largest decrease of type I procollagen mRNAs is observed in the nuclear and cytoplasmic subcellular fractions 24 h after dexamethasone treatment. Type I procollagen hnRNAs are also decreased as determined by Northern blot analysis of total nuclear RNA. The synthesis of total cellular type I procollagen mRNAs is reversibly decreased by dexamethasone treatment. In addition the synthesis of total nuclear type I procollagen mRNA sequences is decreased at 2, 4, and 24 h following the addition of radioactive nucleoside and dexamethasone to cell cultures. Although the synthesis of pro alpha 1(I) and pro alpha 2(I) mRNAs is decreased in dexamethasone-treated chick skin fibroblasts, the degradation of the total cellular procollagen mRNAs is not altered while the degradation of total cellular RNA is stabilized. These data indicate that the dexamethasone-mediated decrease of procollagen synthesis in embryonic chick skin fibroblasts results from the regulation of procollagen gene expression.
D000199:Actins / Q000378:metabolism; D000818:Animals; D002642:Chick Embryo; D003094:Collagen / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D009693:Nucleic Acid Hybridization; D011347:Procollagen / Q000235:genetics*; D011392:Proline / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification; D012332:RNA, Heterogeneous Nuclear / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics*; D012867:Skin / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D000199:Actins; D005938:Glucocorticoids; D011347:Procollagen; D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D012313:RNA; D003907:Dexamethasone; D003094:Collagen; D011392:Proline