Dexamethasone Increases Adenylyl Cyclase Activity and Expression of the Alpha-subunit of Gs in GH3 Cells

Glucocorticoids regulate responsiveness of many different cells and tissues to hormones that act by stimulating adenylyl cyclase. In a rat pituitary cell line, GH3, exposure to dexamethasone (150 mM for 72 h) doubled the specific activity of adenylyl cyclase in membrane extracts, whether the enzyme was stimulated by guanine nucleotides, vasoactive intestinal peptide, or forskolin. Dexamethasone treatment of GH3 cells also caused a 5-fold increase in RNA encoding the alpha-chain of Gs (alpha s) as well as a 2-fold increase in membrane-bound alpha s-polypeptide, measured by either of two assays: 1) Biochemical complementation of the alpha s deficiency of S49 lymphoma cyc- membranes in vitro; 2) Cholera toxin-catalyzed ADP ribosylation of 45- and 52-kilodalton alpha s-polypeptides. These observations suggest that glucocorticoid-induced enhancement of adenylyl cyclase activity in GH3 cells is mediated, at least in part, by increased expression of alpha s.