Distinct transcriptional effects of cAMP on 2 thyroid specific genes: thyroperoxidase and thyroglobulin

The production of the thyroid hormones by the thyroid tissue is regulated by thyrotropin (TSH). TSH, through cAMP, enhances all steps of T3 and T4 synthesis, among which transcription of the genes encoding the precursor protein, thyroglobulin (TG) and the enzyme responsible for the iodination and coupling mechanisms, thyroperoxidase (TPO). Run-on transcription assays show that the kinetics of TG gene transcriptional activation by cAMP is slow (8 to 16 hours) in dog thyrocytes in primary culture, while it is rapid (1 hour) in dog thyroid slices. Activation is sensitive to cycloheximide, reflecting the need for ongoing protein synthesis. In contrast, stimulation of TPO gene transcription is rapid in both experimental systems and is not inhibited in the presence of cycloheximide. It is concluded that different regulatory mechanisms are implicated in the control of Tg and TPO gene transcription by cAMP. However, the stimulation of TG and TPO gene transcription are equally suppressed by inhibition of cAMP-dependent protein kinase, which suggests that both regulatory mechanisms involve protein phosphorylation.