STABILIZATION OF THE MESSENGER-RNA FOR THE UNCOUPLING PROTEIN THERMOGENIN BY TRANSCRIPTIONAL TRANSLATIONAL BLOCKADE AND BY NORADRENALINE INBROWN ADIPOCYTES DIFFERENTIATED IN CULTURE - A DEGRADATION FACTOR-INDUCED BY CESSATION OF STIMULATION/

The stability of the mRNA coding for the uncoupling protein thermogeni n was investigated in mouse brown-fat cells differentiated in culture. After 7 days in culture, the cells were stimulated for 24 h with nora drenaline, and a high level of thermogenin mRNA was then observed. If noradrenaline treatment was continued, the mRNA level remained high, b ut, upon withdrawal of noradrenaline, the level decreased rapidly, wit h a half-life of only 2.7 h. The presence of transcriptional (actinomy cin) or translational (cycloheximide) inhibitors prolonged the apparen t half-life by about 50%. The presence of noradrenaline during transcr iptional blockade led to a further stabilization of thermogenin mRNA. It was concluded that an induced (or short-lived) gene product is impo rtant for thermogenin mRNA degradation. Direct interaction of noradren aline with the cultured brown adipocytes could apparently not mimic th e paradoxical destabilization of thermogenin mRNA in vivo, previously observed in the cold-exposed mouse [Jacobsson, Cannon and Nedergaard ( 1987) FEBS Lett. 224, 353-356], indicating significant differences bet ween the systems in vitro and in vivo.