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Interferon- Inhibits Thyrotropin-Induced Thyroglobulin Gene Transcription in Cultured Human Thyrocytes^*

ANNIE W. C. KUNG and K. S. LAU

Department of Medicine, University of Hong Kong, Queen Mary Hospital Hong Kong

It has been shown that interferon- (IFN) can induce HLA class II antigen expression by thyroid epithelial cells and may play a role in the pathogenesis of autoimmune thyroid disease. We have examined the metabolic effect of recombinant human IFN (0.001-500 U/mL) on thyroglobulin (TG) synthesis and secretion in cultured human thyrocytes. Thyrocytes dispersed from human Graves' thyroid tissues were cultured in the presence of TSH with or without IFN. IFN alone had not effect on either basal TG secretion or de novo TG synthesis, as measured by immunoprecipitation. At 100 U/mL and above, IFN inhibited TSH-induced TG secretion into the medium. At 500 U/mL, IFN inhibited TSH- or dibutyryl cAMP-induced TG synthesis at the gene transcription level, as evidenced by the decrease in steady state TG mRNA. IFN had no effect on either basal or TSH-induced cAMP release by the thyrocytes, suggesting that the inhibitory effect occurs at a site distal to cAMP formation.

These data demonstrate that IFN directly inhibits TSHstimulated TG gene expression and TG secretion. This provides further evidence that IFN has a metabolic effect on thyroid hormone synthesis.

^* This work was supported by CRCG Grant 337/041/0001 and Lee Wing Tat Medical Research Fund (377/030/7809), University of Hong Kong.

To whom all correspondence and requests for reprints should be addressed.

Received December 5, 1989.

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