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Journal of Clinical Endocrinology & Metabolism Vol. 70, No. 6 1512-1517
doi:10.1210/jcem-70-6-1512
Copyright © 1990 by the Endocrine Society.
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Interferon-{gamma} Inhibits Thyrotropin-Induced Thyroglobulin Gene Transcription in Cultured Human Thyrocytes*

ANNIE W. C. KUNG{dagger} and K. S. LAU

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

It has been shown that interferon-{gamma} (IFN{gamma}) 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{gamma} (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{gamma}. IFN{gamma} 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{gamma} inhibited TSH-induced TG secretion into the medium. At 500 U/mL, IFN{gamma} inhibited TSH- or dibutyryl cAMP-induced TG synthesis at the gene transcription level, as evidenced by the decrease in steady state TG mRNA. IFN{gamma} 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{gamma} directly inhibits TSHstimulated TG gene expression and TG secretion. This provides further evidence that IFN{gamma} 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.

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

Received December 5, 1989.




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