Differential Effects of Acute and Chronic Exposure to Interferon-γ on Cyclic Adenosine 3′,5′-Monophosphate Response Element-Regulated Gene Expression1

TSH stimulates proliferation and maintains differentiated function in thyroid follicular cells. The mitogenic activity and the stimulatory effects of TSH on thyroid-specific gene expression are impaired by interferon-γ (IFNγ); however, the mechanisms for these effects have not been elucidated in detail. We examined the effects of IFNγ on acute responses to TSH in rat thyroid cells. IFNγ did not impair TSH-stimulated p70/p85 ribosomal protein S6 kinase (p70/p85s6k) activity or cAMP response element (CRE)-regulated gene expression, although it inhibited DNA synthesis and thyroglobulin expression, effects measured over a more prolonged time course than those on kinase activity and reporter gene expression. Unexpectedly, when cells were chronically exposed to IFNγ, CRE-lacZ promoter activity was decreased, whereas other cAMP-mediated signals, such as p70/p85s6k activity and CRE-binding protein phosphorylation, were unaffected. Activating protein-1-regulated promoters were also impaired by IFNγ treatment, but ...