Triiodothyronine amplifies the adrenergic stimulation of uncoupling protein expression in rat brown adipocytes

Uncoupling protein (UCP), the mitochondrial protein specific to brown adipo se tissue, is activated transcriptionally in response to cold and adrenergi c agents. We studied the role of triiodothyronine (T-3) on the adrenergic s timulation of UCP mRNA expression by use of primary cultures of rat brown a dipocytes. Basal UCP mRNA levels are undetectable. Norepinephrine (NE) incr eases UCP mRNA during differentiation, not during proliferation. In hypothy roid conditions, UCP mRNA response to NE is almost absent. The presence of T-3 (0.2-20 nM) greatly increases the adrenergic response (30-fold). The se nsitivity of UCP mRNA responses to NE is potentiated similar to 100-fold by the presence of TS The effect is proportional to the dose and time of pree xposure to T-3 The increases obtained with NE and T-3 are prevented by acti nomycin and cycloheximide. T-3 greatly stabilizes UCP mRNA transcripts. The effects of thyroxine and retinoic acid are weaker than those of T-3. In co nclusion, in cultured rat brown adipocytes, T-3 is required and both synerg izes with NE to increase UCP mRNA and stabilizes its mRNA transcripts.