CYCLOHEXIMIDE ENHANCES ACTH-RECEPTOR MESSENGER-RNA THROUGH TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MECHANISMS IN BOVINE ADRENOCORTICAL-CELLS

We have previously shown that ACTH is one of the few polypeptide hormo nes having a positive trophic effect, not only on the number, but also on the expression of its own receptors. In the present study, we inve stigated whether the constitutive and ACTH-induced expression of ACTH- receptor (ACTH-R) mRNA in bovine adrenocortical cells (BAC) requires n ew protein synthesis. The results show that cycloheximide alone, an in hibitor of protein synthesis, induced a time- and dose-dependent incre ase in the constitutive level of the ACTH-R major transcript of 3.6 kb in BAG. The maximal stimulation (5.17 +/- 1.15 fold, n = 4) was obtai ned after 24 h treatment with 5 mu g/ml cycloheximide. The effect of c ycloheximide was specific and not directly related to translational ar rest since other protein synthesis inhibitors acting through different mechanisms, emetine and puromycin, were unable to reproduce such an e ffect at concentrations inhibiting protein synthesis. The effect of cy cloheximide involved an increase in the half-life and the transcriptio n rate of the major transcript of ACTH-R (2- and 8.4-fold respectively ). In addition, the results also demonstrated that neither the constit utive nor the ACTH-induced expression of ACTH-R require new protein sy nthesis.