Transcriptional activation of type III inner ring deiodinase by growth factors in cultured rat brown adipocytes

The activity of the type III inner ring deiodinase (DIII), which converts T-4 and T-3 to inactive metabolites, is induced by serum and growth factors in primary cultures of rat brown adipocytes. The contribution of pretranslational mechanisms to this increase in DIII activity was examined in the present studies. DIII mRNA is undetectable in differentiated brown adipocytes when cultured in serum-free medium. However, exposure to epidermal growth factor (EGF), acidic or basic fibroblast growth factors (aFGF or bFGF) increase DIII transcript levels. Lesser inductions are found with platelet-derived growth factor, and insulin-like growth factor I has no effect. Maximal induction of DIII mRNA is obtained after 9 h of exposure to EGF, bFGF, or aFGF at a concentration of 10 ng/ml. The increase in DIII mRNA in response to aFGF, bFGF, and EGF requires gene transcription and protein synthesis, as the inductive effect on mRNA is completely blocked by actinomycin D or cycloheximide. The DIII mRNA half-life is 4 h when stimulated with bFGF and increases to 12 h when 10% serum, EGF, or aFGF is present. In conclusion, EGF, aFGF, and bFGF increase DIII mRNA expression in differentiated brown adipocytes. This effect appears to be exerted at the level of both enhanced transcription and mRNA stabilization.