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

Hernández, Arturo, and Maria Jesús Obregón. Triiodothyronine amplifies the adrenergic stimulation of uncoupling protein expression in rat brown adipocytes. Am J Physiol Endocrinol Metab 278: E769–E777, 2000.—Uncoupling protein (UCP), the mitochondrial protein specific to brown adipose tissue, is activated transcriptionally in response to cold and adrenergic agents. We studied the role of triiodothyronine (T3) on the adrenergic stimulation of UCP mRNA expression by use of primary cultures of rat brown adipocytes. Basal UCP mRNAlevels are undetectable. Norepinephrine (NE) increases UCP mRNA during differentiation, not during proliferation. In hypothyroid conditions, UCP mRNA response to NE is almost absent. The presence of T3 (0.2–20 nM) greatly increases the adrenergic response (30fold). The sensitivity of UCP mRNA responses to NE is potentiated ,100-fold by the presence of T3. The effect is proportional to the dose and time of preexposure to T3. The increases obtained with NE and T3 are prevented by actinomycin and cycloheximide. T3 greatly stabilizes UCP mRNA transcripts. The effects of thyroxine and retinoic acid are weaker than those of T3. In conclusion, in cultured rat brown adipocytes, T3 is required and both synergizes with NE to increase UCP mRNA and stabilizes its mRNA transcripts.