Biological Evidence for Extrathyroidal Thyroxine Formation

Evans, Edward S.; Schooley, Robert A.; Evans, Alison B.; Jenkins, Cecelia A.; Taurog, Alvin

doi:10.1210/endo-78-5-983

Cited by 30 publications

(16 citation statements)

References 13 publications

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“…In the Succulent Karoo, food availability is high in the moist season and striped mice gain body mass in preparation for the subsequent breeding season and to survive the next dry season (Schradin et al, 2014). Many seasonal breeding bird and mammal species utilize thyroid hormones for timing the onset and cessation of reproductive activity (Evans et al, 1966;Hulbert, 2000;Thrun et al, 1996). The negative relationship between RMR and T 3 levels may result from interactions between T 3 and steroid hormones such as testosterone, which are also involved in the regulation of reproduction.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, thyroid hormones regulate seasonal adjustments of body mass, food intake and exercise (Barrett et al, 2007;Ciloglu et al, 2005;Ebling and Barrett, 2008), and are also involved in the timing and cessation of reproduction in seasonal breeders (Billings et al, 2002;Evans et al, 1966;Thrun et al, 1996). Thus, thyroid hormones could enable adaptive physiological responses to environmental and seasonal change.…”

Section: Introductionmentioning

confidence: 99%

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Both thyroid hormone levels and resting metabolic rate decrease in African striped mice when food availability decreases

Rimbach

Pillay

Schradin

2016

Journal of Experimental Biology

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In response to variation in food availability and ambient temperature (T a ), many animals show seasonal adaptations in their physiology. Laboratory studies showed that thyroid hormones are involved in the regulation of metabolism, and their regulatory function is especially important when the energy balance of an individual is compromised. However, little is known about the relationship between thyroid hormones and metabolism in free-living animals and animals inhabiting seasonal environments. Here, we studied seasonal changes in triiodothyronine (T 3 ) levels, resting metabolic rate (RMR) and two physiological markers of energy balance (blood glucose and ketone bodies) in 61 free-living African striped mice (Rhabdomys pumilio) that live in an semi-arid environment with food shortage during the dry season. We predicted a positive relationship between T 3 levels and RMR. Further, we predicted higher T 3 levels, blood glucose levels and RMR, but lower ketone body concentrations, during the moist season when food availability is high compared with summer when food availability is low. RMR and T 3 levels were negatively related in the moist season but not in the dry season. Both RMR and T 3 levels were higher in the moist than in the dry season, and T 3 levels increased with increasing food availability. In the dry season, blood glucose levels were lower but ketone body concentrations were higher, indicating a change in substrate use. Seasonal adjustments in RMR and T 3 levels permit a reduction of energy expenditure when food is scarce, and reflect an adaptive response to reduced food availability in the dry season.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Both thyroid hormone levels and resting metabolic rate decrease in African striped mice when food availability decreases

Rimbach

Pillay

Schradin

2016

Journal of Experimental Biology

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“…However, we propose that the cardiomyocyte-generated hormone serves exclusively intracrine purposes and does not affect the systemic hormone levels that are regulated by the thyroid gland. This hypothesis is also supported by the early reports of extrathyroidal thyroid hormone generation that demonstrated the necessity of high doses for iodide supplementation to be effective (9). Apparently cardiomyocytes under physiological conditions import only minimal amounts of iodide.…”

Section: Discussionmentioning

confidence: 65%

“…However, several studies by the group of Taurog (9,22) and others (16) suggested the possibility of a low-level generation of thyroid hormone in organs/ tissues other than the thyroid gland. Taurog et al (9) demonstrated in thyroidectomized rats that in all indexes of T 4 action examined, namely growth, metabolic rate, heart rate, and pituitary, adrenal and reproductive function, the restorative or maintenance activities of large and repeatedly administrated quantities of iodide were identical with those of minute quantities of T 4 . In a later study of comparable experimental design they showed by scans of paper chromatograms the presence of T 4 in the plasma of the thyroidectomized rats (22).…”

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confidence: 99%

H9c2 cardiomyoblasts produce thyroid hormone

Meischl

Buermans²,

Hazes³

et al. 2008

American Journal of Physiology-Cell Physiology

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hormone acts on a wide range of tissues. In the cardiovascular system, thyroid hormone is an important regulator of cardiac function and cardiovascular hemodynamics. Although some early reports in the literature suggested an unknown extrathyroidal source of thyroid hormone, it is currently thought to be produced exclusively in the thyroid gland, a highly specialized organ with the sole function of generating, storing, and secreting thyroid hormone. Whereas most of the proteins necessary for thyroid hormone synthesis are thought to be expressed exclusively in the thyroid gland, we now have found evidence that all of these proteins, i.e., thyroglobulin, DUOX1, DUOX2, the sodium-iodide symporter, pendrin, thyroid peroxidase, and thyroid-stimulating hormone receptor, are also expressed in cardiomyocytes. Furthermore, we found thyroglobulin to be transiently upregulated in an in vitro model of ischemia. When performing these experiments in the presence of 125 I, we found that 125 I was integrated into thyroglobulin and that under ischemia-like conditions the radioactive signal in thyroglobulin was reduced. Concomitantly we observed an increase of intracellularly produced, 125 I-labeled thyroid hormone. In conclusion, our findings demonstrate for the first time that cardiomyocytes produce thyroid hormone in a manner adapted to the cell's environment. DUOX; cardiomyocyte; ischemia; heart failure THYROID HORMONE influences the basal metabolic rate of a wide range of tissues and is in the cardiovascular system an important regulator of cardiac function and cardiovascular hemodynamics (7). Thyroxine (T 4 ) is the main product of thyroid secretion and is deiodinated in peripheral tissues to triiodothyronine (T 3 ), the biologically active thyroid hormone (3). T 3 either regulates gene expression by binding to high-affinity nuclear receptors that, in turn, recognize specific responseelement sequences in the promoters of T 3 -target genes (11) or exerts different nonnuclear effects by as yet less well characterized mechanisms.In the heart T 3 acts directly on the cardiomyocytes where it stimulates heart rate and contractile performance, the later mediated, to a large extent, by increased expression of the calcium adenosine triphosphatase of the sarcoplasmic reticulum and a decreased expression of phospholamban.Pathophysiologically, T 3 has been shown to be important for the induction of different forms of cardiac hypertrophy (19) and for the response of the heart to ischemic stress (17). The exact mechanisms are still under investigation.Traditionally, the thyroid gland has been considered the sole source of thyroid hormone. However, several studies by the group of Taurog (9, 22) and others (16) suggested the possibility of a low-level generation of thyroid hormone in organs/ tissues other than the thyroid gland. Taurog et al. (9) demonstrated in thyroidectomized rats that in all indexes of T 4 action examined, namely growth, metabolic rate, heart rate, and pituitary, adrenal and reproductive function, the restorative or mai...

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“…The notion of extrathyroidal hormone production is not new with authors from the sixties, and possibly earlier, providing solid evidence for the process (Evans et al 1966, Taurog & Evans 1967, Obregon et al 1981. Most recent evidence reports that in vitro, cardiomyocytes express all of the required components and are able to produce thyroid hormone (Meischl et al 2008).…”

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confidence: 99%

Extrathyroidal thyroid hormone synthesis?

Ludgate

2011

Journal of Endocrinology

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A paper published in this issue of the Journal of Endocrinology has revisited the hypothesis that thyroid hormones may be generated by tissues outside the thyroid gland in higher organisms including mammals. This commentary appraises the strengths and weaknesses of the study, the alternative explanations for the findings and possible future measures to investigate further. The concept of extrathyroidal thyroxine and triiodothyronine synthesis has previously been proposed; by assuming that Nagao et al. and earlier authors are correct, the plausibility and possible mechanisms underlying the hypothesis are discussed.

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Biological Evidence for Extrathyroidal Thyroxine Formation

Cited by 30 publications

References 13 publications

Both thyroid hormone levels and resting metabolic rate decrease in African striped mice when food availability decreases

Both thyroid hormone levels and resting metabolic rate decrease in African striped mice when food availability decreases

H9c2 cardiomyoblasts produce thyroid hormone

Extrathyroidal thyroid hormone synthesis?

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