Palmitic Acid Downregulates Thyroglobulin (Tg), Sodium Iodide Symporter (NIS), and Thyroperoxidase (TPO) in Human Primary Thyrocytes: A Potential Mechanism by Which Lipotoxicity Affects Thyroid?

Our previous studies suggested that the thyroid might be a target organ affected by lipotoxicity, which might be partially related to the increasing prevalence of subclinical hypothyroidism. However, the underlying molecular mechanism is not yet clearly established. This study aimed to assess the effect of palmitic acid stimulation on thyrocyte function. Upon palmitic acid stimulation, intracellular contents of lipids, as well as the expression and activity of three key molecules in thyroid hormone synthesis (i.e., thyroglobulin, sodium iodide symporter, and thyroperoxidase), were determined in human primary thyrocytes. The contents of BODIPY® FL C16 (the fluorescently labeled palmitic acid analogue) entering into the thyrocytes were gradually increased with time extending. Accordingly, the intracellular accumulation of both triglyceride and free fatty acids increased in dose- and time-dependent manners. The effect of palmitic acid stimulation on thyroid hormone synthesis was then determined. Both the mRNA and protein levels of thyroglobulin, sodium iodide symporter, and thyroperoxidase were decreased following palmitic acid stimulation. Consistently, upon palmitic acid stimulation, the secreted thyroglobulin levels in supernatants, 131I uptake, and extracellular thyroperoxidase activity were all decreased in a dose-dependent manner. Our results demonstrated that upon palmitic acid stimulation, the expressions of the key molecules (thyroglobulin, sodium iodide symporter, and thyroperoxidase) were reduced and their activities were suppressed, which might lead to impaired thyroid hormone synthesis.

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Iodide excess regulates its own efflux: a possible involvement of pendrin

AJP Cell Physiology ◽

10.1152/ajpcell.00210.2015 ◽

2016 ◽

Vol 310 (7) ◽

pp. C576-C582 ◽

Cited By ~ 12

Author(s):

Jamile Calil-Silveira ◽

Caroline Serrano-Nascimento ◽

Peter Andreas Kopp ◽

Maria Tereza Nunes

Keyword(s):

Plasma Membrane ◽

Thyroid Hormone ◽

Thyroid Hormones ◽

Sodium Iodide ◽

Inhibitory Effect ◽

Membrane Insertion ◽

Sodium Iodide Symporter ◽

Iodide Uptake ◽

Hormone Synthesis ◽

Rat Thyroid

Adequate iodide supply and metabolism are essential for thyroid hormones synthesis. In thyrocytes, iodide uptake is mediated by the sodium-iodide symporter, but several proteins appear to be involved in iodide efflux. Previous studies demonstrated that pendrin is able to mediate apical efflux of iodide in thyrocytes. Acute iodide excess transiently impairs thyroid hormone synthesis, a phenomenon known as the Wolff-Chaikoff effect. Although the escape from this inhibitory effect is not completely understood, it has been related to the inhibition of sodium-iodide symporter-mediated iodide uptake. However, the effects of iodide excess on iodide efflux have not been characterized. Herein, we investigated the consequences of iodide excess on pendrin abundance, subcellular localization, and iodide efflux in rat thyroid PCCl3 cells. Our results indicate that iodide excess increases pendrin abundance and plasma membrane insertion after 24 h of treatment. Moreover, iodide excess increases pendrin half-life. Finally, iodide exposure also increases iodide efflux from PCCl3 cells. In conclusion, these data suggest that pendrin may have an important role in mediating iodide efflux in thyrocytes, especially under conditions of iodide excess.

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Resveratrol Alleviates the Inhibitory Effect of Tunicamycin-Induced Endoplasmic Reticulum Stress on Expression of Genes Involved in Thyroid Hormone Synthesis in FRTL-5 Thyrocytes

International Journal of Molecular Sciences ◽

10.3390/ijms22094373 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4373

Author(s):

Gaiping Wen ◽

Klaus Eder ◽

Robert Ringseis

Keyword(s):

Transcription Factor ◽

Thyroid Hormone ◽

Er Stress ◽

Combined Treatment ◽

Thyroid Peroxidase ◽

Sodium Iodide Symporter ◽

Hormone Synthesis ◽

Thyroid Hormone Synthesis ◽

Expression Of Genes ◽

Thyroid Transcription Factor

Recently, ER stress induced by tunicamycin (TM) was reported to inhibit the expression of key genes involved in thyroid hormone synthesis, such as sodium/iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), and their regulators such as thyrotropin receptor (TSHR), thyroid transcription factor-1 (TTF-1), thyroid transcription factor-2 (TTF-2) and paired box gene 8 (PAX-8), in FRTL-5 thyrocytes. The present study tested the hypothesis that resveratrol (RSV) alleviates this effect of TM in FRTL-5 cells. While treatment of FRTL-5 cells with TM alone (0.1 µg/mL) for 48 h strongly induced the ER stress-sensitive genes heat shock protein family A member 5 (HSPA5) and DNA damage inducible transcript 3 (DDIT3) and repressed NIS, TPO, TG, TSHR, TTF-1, TTF-2 and PAX-8, combined treatment with TM (0.1 µg/mL) and RSV (10 µM) for 48 h attenuated this effect of TM. In conclusion, RSV alleviates TM-induced ER stress and attenuates the strong impairment of expression of genes involved in thyroid hormone synthesis and their regulators in FRTL-5 thyrocytes exposed to TM-induced ER stress. Thus, RSV may be useful for the treatment of specific thyroid disorders, provided that strategies with improved oral bioavailability of RSV are applied.

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BIOCHEMICAL DEFECTS IN THYROID HORMONE SYNTHESIS AND THEIR RELATION TO ENDEMIC GOITER

Acta Endocrinologica ◽

10.1530/acta.0.074s034 ◽

1973 ◽

Vol 74 (2_Suppla) ◽

pp. S34-S44

Author(s):

Leslie J. DeGroot

Keyword(s):

Thyroid Hormone ◽

Endemic Goiter ◽

Hormone Synthesis ◽

Thyroid Hormone Synthesis

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THE INFLUENCE OF THE PLASMA INORGANIC IODINE CONCENTRATION ON THYROID FUNCTION IN DEHALOGENASE DEFICIENCY

Acta Endocrinologica ◽

10.1530/acta.0.0550361 ◽

1967 ◽

Vol 55 (2) ◽

pp. 361-368 ◽

Cited By ~ 3

Author(s):

R. McG. Harden ◽

W. D. Alexander ◽

S. Papadopoulos ◽

M. T. Harrison ◽

S. Macfarlane

Keyword(s):

Thyroid Hormone ◽

Thyroid Function ◽

Iodine Concentration ◽

Rapid Rise ◽

Normal Range ◽

Hormone Synthesis ◽

Thyroid Hormone Synthesis ◽

Iodine Metabolism ◽

Inorganic Iodine ◽

Circulating Levels

ABSTRACT Iodine metabolism and thyroid function were studied in a patient with hypothyroidism and goitre due to dehalogenase deficiency. Initially the plasma inorganic iodine (PII) level was within the normal range but circulating levels of hormone were low and the thyroid clearance and absolute uptake of iodine (AIU) by the thyroid were high. Administration of iodide supplements resulted in a rapid rise in the plasma thyroxine concentration and restoration of the euthyroid state. Thyroid hormone synthesis appeared to proceed normally when the PII exceeded 1.0 μg/100 ml. This was achieved by increasing the intake of iodide by 612 μg per day. At PII levels around 10 μg/100 ml there was evidence of increased levels of circulating thyroid hormone.

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