Cycloheximide inhibition of hormonal induction of alpha 2u-globulin mRNA.
The induction of hepatic alpha 2u-globulin synthesis by glucocorticoids in isolated hepatocytes occurs via an increase in the level of its mRNA as measured by cell-free translation and by hydbridization to an alpha 2u-globulin cDNA probe. To explore whether induction of this mRNA is a direct or an indirect consequence of the interaction of the dexamethasone-receptor complex with the alpha 2u-globulin genome, the requirement for ongoing protein synthesis was examined. Concentrations of cycloheximide too low to prevent precursor incorporation into total poly(A)-containing RNA do prevent the hormonal induction of alpha 2u-globulin mRNA. Furthermore, incorporation of 3H-labeled amino acids into total protein was decreased by only 40-50%, and the appearance of the dexamethasone-induced glycosylated forms of alpha 2u-globulin was completely prevented in these cycloheximide-treated hepatocytes. The results suggest that the synthesis of a protein mediator(s) may be required for the induction of alpha 2u-globulin mRNA by glucocorticoids and that the steroid-receptor complex may not interact directly with the alpha 2u-globulin genome.
D000510:Alpha-Globulins / Q000096:biosynthesis*; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011061:Poly A / Q000096:biosynthesis; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*
D000510:Alpha-Globulins; D012333:RNA, Messenger; D011061:Poly A; D003907:Dexamethasone; D003513:Cycloheximide