Control of thyroperoxidase and thyroglobulin transcription by cAMP: evidence for distinct regulatory mechanisms

The expression of the genes coding for thyroglobulin (TG), and thyroperoxidase (TPO), are regulated by TSH. These effects are mediated by cAMP as they are reproduced by forskolin. In vitro run-on transcription assays performed on nuclei isolated from dog thyrocytes in culture or from dog thyroid slices, indicate that the forskolin-induced transcriptional stimulation of TG and TPO genes are very different. For the TG gene, the kinetics of transcriptional activation vary according to the experimental model: it is rapid (1 h) in thyroid slices and slow (8 h) in primary cultures. In contrast, TPO induction is rapid in both cases. In primary cultures, insulin is responsible for the basal level and for a part of forskolin-induced TG transcription, whereas TPO transcription is not affected by insulin. The forskolin-induced increase of TG transcription requires ongoing protein synthesis, as it is blocked by cycloheximide. TPO gene transcription is unaffected by cycloheximide. Taken together with previous data on the two genes, our results suggest that while TPO regulation corresponds to the classical model of genes in which the promoter is regulated directly via cAMP regulatory elements, TG gene regulation involves the synthesis of an intermediary, rapid turnover trans-acting protein.