GLUCOCORTICOSTEROIDS INCREASE BETA(2)-ADRENERGIC RECEPTOR TRANSCRIPTION IN HUMAN LUNG

beta(2)-Adrenergic receptors (beta(2)R) are widely distributed and med iate a wide range of cellular responses in lung. Because glucocorticos teroids increase expression of beta(2)R in cell lines, we have investi gated the effects of glucocorticoids on the beta(2)R mRNA level and th e number of beta(2)R in human peripheral lung in vitro. Incubation of lung tissues with dexamethasone (Dex) elevated both beta(2)R mRNA leve l (as measured by Northern blot analysis) and beta(2)R number (as meas ured by [I-125]iodocyanopindolol binding). The increased accumulation of beta(2)R mRNA could be detected at 15 min (1.27 +/- 0.1-fold) and t he maximal accumulation occurred at 2 h (2.73 +/- 0.5-fold). The Dex-i nduced increase in beta(2)R mRNA returned to the control level by 17 h . The increase in beta(2)R number (1.58 +/- 0.2-fold) was slower, reac hing a maximum between 17 and 24 h. Dex increased beta(2)R mRNA in a t ime- and concentration-dependent manner that was abolished by the ster oid receptor antagonist mifepristone (RU-38486 or RU-486). The stabili ty of beta(2)R mRNA was unchanged by Dex, and a nuclear run-on assay r evealed that Dex approximately doubled the transcriptional rate of the beta(2)R gene. These observations suggest that glucocorticoids act on steroid receptors to increase beta(2)R expression by increasing the r ate of beta(2)R gene transcription.