scholarly journals Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Eleonore Fröhlich ◽  
Richard Wahl
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Virus Disease ◽  
Physiological Role ◽  
Promising Candidate ◽  
Reverse T3 ◽  
Metabolic Dysregulation ◽  
Main Effects ◽  
Potential Use

Thyroxine and triiodothyronine (T3) are classical thyroid hormones and with relatively well-understood actions. In contrast, the physiological role of thyroid hormone metabolites, also circulating in the blood, is less well characterized. These molecules, namely, reverse triiodothyronine, 3,5-diiodothyronine, 3-iodothyronamine, tetraiodoacetic acid and triiodoacetic acid, mediate both agonistic (thyromimetic) and antagonistic actions additional to the effects of the classical thyroid hormones. Here, we provide an overview of the main factors influencing thyroid hormone action, and then go on to describe the main effects of the metabolites and their potential use in medicine. One section addresses thyroid hormone levels in corona virus disease 19 (COVID-19). It appears that i) the more potently-acting molecules T3 and triiodoacetic acid have shorter half-lives than the less potent antagonists 3-iodothyronamine and tetraiodoacetic acid; ii) reverse T3 and 3,5-diiodothyronine may serve as indicators for metabolic dysregulation and disease, and iii) Nanotetrac may be a promising candidate for treating cancer, and resmetirom and VK2809 for steatohepatitis. Further, the use of L-T3 in the treatment of severely ill COVID-19 patients is critically discussed.

Thyroid hormone dependent nuclear proteins from rat liver

1982 ◽  
Vol 99 (4) ◽  
pp. 567-572
Author(s):  
Angeles Rodriguez-Pena ◽  
Juan Bernal
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Effective Dose ◽  
Rat Liver ◽  
Physiological Role ◽  
Nuclear Proteins ◽  
Single Administration ◽  
Minimum Effective Dose ◽  
Nuclear Level

Abstract. Two nuclear proteins from rat liver were shown to be dependent on thyroid hormones. These proteins were present in the nucleosol or nucleoplasmic fraction, and were extracted from the nuclei with 0.15 m NaCl at pH8. After thyroidectomy, a 120 000-Mr polypeptide decreased in concentration to levels below 10% of normal control rats and another polypeptide of 81 000-Mr was increased. Treatment with T4 at physiological replacement doses for several days restored the levels of both proteins to normal. A single administration of 50 μg T3 induced a detectable increase of 120K after 14 h, with maximal effects at 48 h after administration. The minimum effective dose of T3 on 120K was 0.5 μg administered for three days. Preliminary observations suggest that the response of 81K to thyroid hormones is much more sensitive than that of 120K. The physiological role of these polypeptides is unknown, but they could be involved in the mode of T3 action at the nuclear level.

Thyroid hormone control of Na+-K+-ATPase and K+-dependent phosphatase in rat heart

1977 ◽  
Vol 232 (5) ◽  
pp. C196-C201 ◽  
Author(s):  
K. D. Philipson ◽  
I. S. Edelman
Keyword(s):  
Thyroid Hormone ◽  
Atpase Activity ◽  
Weight Ratio ◽  
Heart Weight ◽  
Reverse T3 ◽  
Na Pump ◽  
Hormone Control ◽  
Rat Ventricle

To assess the possible role of the Na+ pump in mediating physiological responses to thyroid hormone in the rat myocardium, we examined the effects of L-3,5,3'-triiodothyronine (T3) on the activities of the closely associated enzymes, Na+-K+-dependent adenosine triphosphatase (Na-K-ATPase) and K+-dependent p-nitrophenyl phosphatase (K-dep-pNPPase). In hypothyroid rats, administration of T3 (50 microng/100 g body wt) resulted in significant increases (greater than 50%) in Na-K-ATPase and K-dep-pNPPase activities in both crude homogenates and microsomal fractions of the rat ventricle. Significant effects on Na-K-ATPase activity were also attained with low doses (1 microng/100 g body wt) of T3. A method was developed for assaying K-dep-pNPPase activity in cardiac slices. With this technique, enhancement in K-dep-pNPPase activity of 89.2% was found in ventricle slices after treatment of hypothyroid rats with T3 (50 microng/100 g body wt), implying that augmentation of the capacity of the Na+ pump is achieved in vivo. The potent analogue, L-3,5-diiodo-3' isopropyl thyronine (isopropyl T2) had the same effects on cardiac growth and Na-K-ATPase as T3, in hypothyroid rats. In contrast, the relatively inactive isomer, L-3,3',5'-triiodothyronine (reverse T3) had no significant effect on the heart weight-to-body weight ratio or on ventricular Na-K-ATPase activity.

scholarly journals Role of reduced thyroid hormone status on bone mineral metabolism

2021 ◽  
Vol 19 (2) ◽  
pp. 26-29
Author(s):  
X Lourdes Sandy ◽  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Bone Mineral ◽  
Serum Calcium ◽  
Mineral Metabolism ◽  
Bone Mineral Metabolism ◽  
Hormone Status ◽  
Calcium And Phosphorus ◽  
Hypothyroid Patients

Background: The most common endocrine disorder is hypothyroidism which accounts to 11%. Thyroid hormones have a wide array of functions such as physiological growth and development of skeletal system, maintenance of basal metabolic rate and regulation of various metabolisms, including mineral metabolism. Nowadays due to its direct action on bone turn over, thyroid hormones are considered to have an important role on bone mineral metabolism. Thyroid disorders are important cause for secondary osteoporosis. So the present study was done to know the levels of bone minerals, calcium and phosphorus in hypothyroidism and its relation with thyroid hormone levels. Methods: A case-control study was conducted on 30 hypothyroid patients and 30 euthyroid healthy controls in the age group of 20-60 years. Blood samples were collected from all the study population. Serum total triiodothyronine, total thyroxine and TSH by Enzyme-Linked Immunosorbent Assay, Serum calcium by Arsenazo III method, phosphorous by ammonium molybdate method were estimated. Results: Serum calcium levels in cases was found to significantly reduced when compared to controls (p<0.001). Serum phosphorous levels also showed considerable elevation in cases when compared to controls (p<0.001). There was a significant negative correlation between TSH and serum calcium in cases. Conclusion: The present study indicated the important role of reduced thyroid hormone status on bone mineral metabolism. This study concludes that serum calcium was significantly reduced and phosphorus levels were significantly increased in hypothyroid patients when compared to euthyroid control subjects. So frequent monitoring of serum calcium and phosphorus in hypothyroid patients would reduce the burden of bone pathologies.

scholarly journals Demonstration of reciprocal diurnal variation in human serum T3 and rT3 concentration demonstrated by mass spectrometric analysis and establishment of thyroid hormone reference intervals

2020 ◽  
Vol 11 ◽  
pp. 204201882092268
Author(s):  
Qian Sun ◽  
Lívia Avallone ◽  
Brian Stolze ◽  
Katherine A. Araque ◽  
Yesim Özarda ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Reference Intervals ◽  
Diurnal Fluctuation ◽  
Spectrometric Analysis ◽  
Serum Samples ◽  
Free Triiodothyronine ◽  
Reverse T3 ◽  
Wide Range ◽  
Total Thyroxine

Background: There has been a wide range of reference intervals proposed in previous literature for thyroid hormones due to large between-assay variability of immunoassays, as well as lack of correction for collection time. We provided the diurnal reference intervals for five thyroid hormones, namely total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and reverse T3 (rT3), measured in serum samples of healthy participants using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Methods: Couplet serum samples (a.m. and p.m.) were collected from 110 healthy females and 49 healthy males. Healthy volunteers were recruited from four participating centers between 2016 and 2018. Measurements of thyroid hormones were obtained by LC-MS/MS analysis. Results: Our study revealed significant uptrend in AM to PM FT4 ( p < 0.0001) samples, downtrend in AM to PM TT3 ( p = 0.0004) and FT3 samples ( p < 0.0001), and AM to PM uptrend in rT3 samples ( p < 0.0001). No difference was observed for TT4 between AM and PM. No significant sex differences were seen for any of the five thyroid hormones. Conclusion: When diagnosing thyroid disorders, it is important to have accurate measurement of thyroid hormones, and to acknowledge the diurnal fluctuation found, especially for FT3. Our study highlights the importance of standardization of collection times and implementation of LC-MS/MS in thyroid hormone measurement.

Manipulation of thyroid hormones in ruminants - a tool to understand their physiological role and identify their potential for increasing production efficiency

2002 ◽  
Vol 53 (3) ◽  
pp. 259 ◽  
Author(s):  
D. Villar ◽  
S. M. Rhind ◽  
J. R. Arthur ◽  
P. J. Goddard
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Production Efficiency ◽  
Hormone Replacement ◽  
Animal Health ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Physiological Role ◽  
Antithyroid Drugs ◽  
Few Data

Manipulations of thyroid hormone secretion and function can be used to cure thyroidal deficiencies or overactivity and as a tool to investigate their physiological roles and identify potential protocols for enhancing animal performance. An essential approach to the investigation of thyroid hormone action involves the induction of hypothyroidal states. Methods of inducing hypothyroidal states in ruminants include thyroidectomy and treatment with thionamides. There are few data concerning the induction of an optimal degree of hypothyroidism for the study of thyroid function in ruminants, unlike the situation in rodents. The effects of hypothyroidism on the physiology of ruminants, and the relative merits of thyroidectomy or of treatment with thionamides to manipulate thyroid hormone profiles in them, are reviewed and discussed. Thyroidectomy in ruminants induces an acute, irreversible, hypothyroidal state. It also has indirect, predominantly adverse, effects on many physiological processes and impairs health. Thus, thyroidectomised (THX) animals cannot be sustained for long-term studies without thyroid hormone replacement. Antithyroid drugs of the thionamide class, on the other hand, have been used with success to induce varying degrees of hypothyroidism, predominantly less severe than those induced by thyroidectomy. The changes induced by drugs are reversible upon withdrawal of treatment. However, treatment may require daily administration of the drug for several weeks before stable plasma concentrations of thyroid hormone are achieved. Furthermore, at high doses, these drugs can have toxic side effects. It is concluded that the treatment regime of choice will depend on the objectives of the individual study. Knowledge of the activities of thyroid hormone metabolising, deiodinase enzymes in the target tissues is also required if the actions of some of these drugs, their physiological roles in modulation of the thyroid hormones, and, crucially, their potential effects on animal health and production are to be properly understood and exploited.

Effects of hypo- and hyperthyroidism on pancreatic TRH-degrading activity and TRH concentrations in developing rat pancreas

1984 ◽  
Vol 106 (2) ◽  
pp. 209-214 ◽  
Author(s):  
Sonia Aratan-Spire ◽  
Bryan Wolf ◽  
Paul Czernichow
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Neonatal Period ◽  
Fold Increase ◽  
Thyroid Status ◽  
Thyrotrophin Releasing Hormone ◽  
Rat Pancreas ◽  
High Concentrations ◽  
Developing Rat

Abstract. High concentrations of thyrotrophin-releasing hormone (TRH) in the rat pancreas were detected during the first few days of life decreasing thereafter while pancreatic TRH-degrading activity (TRH-DA) absent at birth appeared on day 14 and increased to reach adult values by day 21. This period of life is also remarkable by the low level of circulating thyroid hormones. Since TRH-degrading activity may be thyroid hormone dependent it was of interest to study the effects of thyroid status fluctuations both on TRH-DA and TRH content during the neonatal period. In this study, hypo- and hyperthyroidism were induced by 6-n-propyl-2-thiouracil (PTU) and triiodothyronine (T3) respectively. Pancreatic TRH-DA and TRH concentrations were measured at different ages from birth until day 29, in treated animals and results compared to control age-matched rats. In hypothyroid rats, pancreatic TRH concentrations remained significantly higher after day 16 while TRH-DA was lower during the whole period studied. Following T3 treatment, pancreatic TRH concentrations decreased significantly from day 3 onwards. However, no significant changes were found for TRH-DA except a two-fold increase on day 28. These results suggest that two different mechanisms may account for thyroid hormones action: 1) a direct effect on pancreatic TRH 2) an inductive saturable effect on TRH-DA. Furthermore a fine tuner modulatory role of TRH-DA on TRH concentrations cannot be excluded.

scholarly journals Clinical implications of altered thyroid status in male testicular function

2009 ◽  
Vol 53 (8) ◽  
pp. 976-982 ◽  
Author(s):  
Simone Magagnin Wajner ◽  
Márcia Santos Wagner ◽  
Ana Luiza Maia
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Thyroid Status ◽  
Testicular Cells ◽  
Current Review ◽  
Human Spermatogenesis ◽  
Altered Thyroid ◽  
And Function ◽  
The Impact

Thyroid hormones are involved in the development and maintenance of virtually all tissues. Although for many years the testis was thought to be a thyroid-hormone unresponsive organ, studies of the last decades have demonstrated that thyroid dysfunction is associated not only with abnormalities in morphology and function of testes, but also with decreased fertility and alterations of sexual activity in men. Nowadays, the participation of triiodothyronine (T3) in the control of Sertoli and Leydig cell proliferation, testicular maturation, and steroidogenesis is widely accepted, as well as the presence of thyroid hormone transporters and receptors in testicular cells throughout the development process and in adulthood. But even with data suggesting that T3 may act directly on these cells to bring about its effects, there is still controversy regarding the impact of thyroid diseases on human spermatogenesis and fertility, which can be in part due to the lack of well-controlled clinical studies. The current review aims at presenting an updated picture of recent clinical data about the role of thyroid hormones in male gonadal function.

Thyroid hormones and brain development

1995 ◽  
Vol 133 (4) ◽  
pp. 390-398 ◽  
Author(s):  
Juan Bernal ◽  
Jacques Nunez
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Brain Development ◽  
Neuronal Differentiation ◽  
Cell Biology ◽  
Physiological Role ◽  
Hormone Deficiency ◽  
Mammalian Brain

Bernal J, Nunez J. Thyroid hormones and brain development. Eur J Endocrinol 1995;133:390–8. ISSN 0804–4643 Thyroid hormone is a major physiological regulator of mammalian brain development. Cell differentiation, migration and gene expression are altered as a consequence of thyroid hormone deficiency or excess. The physiological role of thyroid hormone can perhaps be defined so as to ensure the timed coordination of different developmental events through specific effects on the rate of cell differentiation and gene expression. All triiodothyronine (T3) receptor isoforms are expressed in the brain and their spatial and temporal patterns of expression suggest unique and complementary functions for the different isoforms. Cell biology studies suggest a role for T3 and its receptors in oligodendroglial and neuronal differentiation and the control of cell death. Some of the effects on neuronal differentiation might be due to an action of thyroid hormone on the production of neurotropins and their receptors. In recent years a number of T3-dependent genes have been identified in the rat brain, such as myelin protein-encoding genes or specific neuronal genes, and thyroid hormone-responsive elements have been demonstrated in some of these genes. The identification of the gene network regulated by thyroid hormone during brain development, the elucidation of the mechanism of regulation and the clarification of the physiological roles of the regulated genes remain major goals for future studies. Jacques Nunez, INSERM U282. Hôpital Henri Mondor, 94010 Créteil, France

scholarly journals Unravelling the role of thyroid hormones in seasonal neuroplasticity in European Starlings (Sturnus vulgaris)

2021 ◽  
Author(s):  
Jasmien EMJ Orije ◽  
Sander R Raymaekers ◽  
Gaurav Majumadar ◽  
Geert De Groof ◽  
Elisabeth Jonckers ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Plasma Concentrations ◽  
Active Role ◽  
Fine Tuning ◽  
European Starlings ◽  
Photosensitive Period ◽  
Song Control

Thyroid hormones clearly play a role in the seasonal regulation of reproduction, but any role they might play in song behavior and the associated seasonal neuroplasticity in songbirds remains to be elucidated. To pursue this question, we first established seasonal patterns in the expression of thyroid hormone regulating genes in male European starlings employing in situ hybridization methods. Thyroid hormone transporter LAT1 expression in the song nucleus HVC was elevated during the photosensitive phase, pointing towards an active role of thyroid hormones during this window of possible neuroplasticity. In contrast, DIO3 expression was high in HVC during the photostimulated phase, limiting the possible effect of thyroid hormones to maintain song stability during the breeding season. Next, we studied the effect of hypothyroidism on song behavior and neuroplasticity using in vivo MRI. Hypothyroidism inhibited the photostimulation-induced increase in testosterone, confirming the role of thyroid hormones in activating the hypothalamic-pituitary-gonadal (HPG) axis. Surprisingly, apart from the myelination of several tracts during the photostimulated phase, most neuroplasticity related to song production was unaffected by hypothyroidism. Remarkably, T3 plasma concentrations were negatively correlated to the microstructural changes in several song control nuclei. Potentially, a global reduction of circulating thyroid hormones during the photosensitive period is necessary to lift the brake imposed by the photorefractory period, whereas local fine-tuning of thyroid hormone concentrations through LAT1 could activate underlying neuroplasticity mechanisms. Given the complexity of thyroid hormone effects, this study is a steppingstone to disentangle the influence of thyroid hormones on seasonal neuroplasticity.

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