The Microsomal/Peroxidase Antigen: Modulation of its Expression in Thyroid Cells

Abstract

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.

Cysteine Proteinases Mediate Extracellular Prohormone Processing in the Thyroid

“…However, it has also been described that a stimulation of thyroid epithelial cells with TSH results in a redistribution of lysosomes from the basal to the apical pole, a phenomenon which has been observed long ago (Seljelid, 1967) and was confirmed in a later analysis (Uchiyama et al, 1989). Furthermore, it has been discussed that the stimulatory effect of TSH on thyroid epithelial cells involves a second major intracellular signalling system, i. e. the phosphatidylinositol cascade, leading to a rise in intracellular Ca 2+ -levels (Chiovato and Pinchera, 1991;Dumont et al, 1992). In many cell types, a rise in intracellular free Ca 2+ seems to trigger fusion of lysosomes with the plasma membrane (Andrews, 2000).…”

Review: Cysteine Proteinases Mediate Extracellular Prohormone Processing in the Thyroid

“…Up to now, this short-term effect of TSH, /'. e. the phosphatidylinositol cascade, leading to a rise in intracellular Ca 2+ -levels (Chiovato and Pinchera, 1991 ;Dumont et al, 1992). However, it has also been described that a stimulation of thyroid epithelial cells with TSH results in a redistribution of lysosomes from the basal to the apical pole, a phenomenon which has been observed long ago (Seljelid, 1967) and was confirmed in a later analysis (Uchiyama et al, 1989).…”

Preferential megalin-mediated transcytosis of low-hormonogenic thyroglobulin: A control mechanism for thyroid hormone release

“…Low-hormonogenic rat Tg (low-horm-rTg) was obtained from media of FRTL-5 cells (American Type Culture Collection, Rockville, MD), as described (15). Thus, FRTL-5 cells, a differentiated rat thyroid cell line (16), are unable to form hormone residues within endogenously synthesized Tg (17). By SDS͞PAGE and Western blotting (WB), Tgs resolved as 660-and 330-kDa bands.…”