The microsomal/peroxidase antigen: modulation of its expression in thyroid cells.
Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular cAMP accumulation and protein synthesis. These data have been found true in any thyroid system studied so far, both in terms of immunologic and enzymatic activity of TPO. TSH and cAMP also increase the levels of the specific mRNA for TPO in thyroid cells from different species. Whether this phenomenon is due to a direct transcriptional regulation of the TPO gene, as shown in dog thyroid cells, or to posttranscriptional effects, as it would appear in FRTL-5 cells, remains to be clarified by future experiments. Thyroid stimulating antibody (TSAb) of Graves' disease also stimulates the expression of M/TPO-Ag. This finding gives further support to the relevance of TSAb in the pathogenesis of hyperthyroidism and explains the well known observation that the "microsomal" antigen is particularly abundant in glands of Graves' patients. The modulation of M/TPO-Ag surface expression by TSH can explain the decrease of circulating anti-MAb observed during L-thyroxine therapy in hypothyroid patients with Hashimoto's thyroiditis. Other agents, such as methimazole and sodium iodide, which influence thyroid cell function, do not directly interfere with the expression of M/TPO-Ag. Cytokines, such as gamma-interferon, interleukin-1, and interleukin-6 have been shown to inhibit the TSH-induced increase of TPO mRNA, but further investigations are required to elucidate the exact role of cytokines in the regulation of M/TPO-Ag expression.
Chiovato
L
L
Istituto di Endocrinologia, University of Pisa, Tirrenia, Italy.
Pinchera
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000032:analysis* / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007453:Iodide Peroxidase / Q000276:immunology*; D033862:Iron-Binding Proteins; D008969:Molecular Sequence Data; D013961:Thyroid Gland / Q000276:immunology*; D013972:Thyrotropin / Q000378:metabolism
D001324:Autoantigens; D033862:Iron-Binding Proteins; D013972:Thyrotropin; D000242:Cyclic AMP; C056658:TPO protein, human; D007453:Iodide Peroxidase