scholarly journals Halogen bonding from the bonding perspective with considerations for mechanisms of thyroid hormone activation and inhibition

2018 ◽  
Vol 42 (13) ◽  
pp. 10623-10632 ◽  
Author(s):  
Craig A. Bayse
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Halogen Bonding ◽  
Thyroid Activity ◽  
Iodothyronine Deiodinase

Bonding models of halogen bonding help understand how thyroid hormones and xenobiotic inhibitors affect thyroid activity through iodothyronine deiodinase.

Regulation of Mammary Gland Sensitivity to Thyroid Hormones During the Transition from Pregnancy to Lactation

2008 ◽  
Vol 233 (10) ◽  
pp. 1309-1314 ◽  
Author(s):  
A. V. Capuco ◽  
E. E. Connor ◽  
D. L. Wood
Keyword(s):  
Mammary Gland ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Thyroid Hormone Receptor ◽  
Physiological State ◽  
Expression Patterns ◽  
Type I ◽  
Hormone Activity ◽  
Iodothyronine Deiodinase ◽  
Copy Numbers

Thyroid hormones are galactopoietic and help to establish the mammary gland’s metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of cows at 53, 35, 20, and 7 days before expected parturition, and 14 and 90 days into the subsequent lactation. Transcript abundance for the three isoforms of iodothyronine deiodinase, type I ( DIO1), type II ( DIO2) and type III ( DIO3), thyroid hormone receptors alpha1 ( TRα 1), alpha2 ( TRα 2) and beta1 ( TRβ 1), and retinoic acid receptors alpha ( RXRα) and gamma ( RXRγ), which act as coregulators of thyroid hormone receptor action, were evaluated by quantitative RT-PCR. The DIO3 is a 5-deiodinase that produces inactive iodothyronine metabolites, whereas DIO1 and DIO2 generate the active thyroid hormone, triiodothyronine, from the relatively inactive precursor, thyroxine. Low copy numbers of DIO3 transcripts were present in mammary gland and liver. DIO2 was the predominant isoform expressed in mammary gland and DIO1 was the predominant isoform expressed in liver. Quantity of DIO1 mRNA in liver tissues did not differ with physiological state, but tended to be lowest during lactation. Quantity of DIO2 mRNA in mammary gland increased during lactation ( P < 0.05), with copy numbers at 90 days of lactation 6-fold greater than at 35 and 20 days prepartum. When ratios of DIO2/DIO3 mRNA were evaluated, the increase was more pronounced (>100-fold). Quantity of TRβ 1 mRNA in mammary gland increased with onset of lactation, whereas TRα 1 and TRα 2 transcripts did not vary with physiological state. Conversely, quantity of RXRα mRNA decreased during late gestation to low levels during early lactation. Data suggest that increased expression of mammary TRβ 1 and DIO2, and decreased RXRα, provide a mechanism to increase thyroid hormone activity within the mammary gland during lactation.

scholarly journals Thyroid hyperactivity with high thyroglobulin in serum despite sufficient iodine intake in chronic cold adaptation in an Arctic Inuit hunter population

2012 ◽  
Vol 166 (3) ◽  
pp. 433-440 ◽  
Author(s):  
Stig Andersen ◽  
Kent Kleinschmidt ◽  
Bodil Hvingel ◽  
Peter Laurberg
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Cold Exposure ◽  
Cold Adaptation ◽  
Urinary Iodine ◽  
Thyroid Activity ◽  
East Greenland ◽  
Brown Adipose ◽  
Iodine Excretion ◽  
The Impact

ObjectiveAdult man hosts brown adipose tissue with the capacity to consume energy and dissipate heat. This is essential for non-shivering thermogenesis and its activation depends on sympathetic activity and thyroid hormones. This led us to evaluate the impact of chronic cold exposure on thyroid activity and thyroid hormones in serum in Arctic residents.DesignComparative, population-based study (n=535) performed in Greenland.MethodsHunters were compared with other men, and Inuit in remote settlements in East Greenland with no modern housing facilities were compared with the residents of the capital city in West Greenland and residents of a major town in East Greenland in a cross-sectional study. We used interview-based questionnaires, measured TSH, free thyroxine, free triiodothyronine (fT3), thyroglobulin (TG) antibody and TG (a measure of thyroid activity) in serum, and iodine and creatinine in spot urine samples.ResultsSerum TG was the highest among hunters (P=0.009) and settlement dwellers (P=0.001), who were most markedly exposed to cold, even though they had the highest urinary iodine excretion (hunters,P<0.001; settlement dwellers,P<0.001). Hunters and settlement dwellers also had the lowest fT3(hunters,P<0.001; settlement dwellers,P<0.001) after adjusting for gender, age, smoking habits, alcohol intake and iodine excretion in multivariate linear regression models. TSH was not influenced by measures of cold exposure (hunter,P=0.36; residence,P=0.91).ConclusionsCold exposure influenced thyroid hormones and TG in serum in Arctic populations consistent with consumption of thyroid hormone and higher thyroid hormone turnover. Findings emphasise that changes in thyroid activity are essential in cold adaptation in Arctic residents.

scholarly journals Consequences of Monocarboxylate Transporter 8 Deficiency for Renal Transport and Metabolism of Thyroid Hormones in Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 802-809 ◽  
Author(s):  
Marija Trajkovic-Arsic ◽  
Theo J. Visser ◽  
Veerle M. Darras ◽  
Edith C. H. Friesema ◽  
Bernhard Schlott ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Psychomotor Retardation ◽  
High Serum ◽  
Monocarboxylate Transporter ◽  
Iodothyronine Deiodinase ◽  
Serum T4 ◽  
Mct8 Deficiency ◽  
Low Serum

Patients carrying inactivating mutations in the gene encoding the thyroid hormone transporting monocarboxylate transporter (MCT)-8 suffer from a severe form of psychomotor retardation and exhibit abnormal serum thyroid hormone levels. The thyroidal phenotype characterized by high-serum T3 and low-serum T4 levels is also found in mice mutants deficient in MCT8 although the cause of these abnormalities is still unknown. Here we describe the consequences of MCT8 deficiency for renal thyroid hormone transport, metabolism, and function by studying MCT8 null mice and wild-type littermates. Whereas serum and urinary parameters do not indicate a strongly altered renal function, a pronounced induction of iodothyronine deiodinase type 1 expression together with increased renal T3 and T4 content point to a general hyperthyroid state of the kidneys in the absence of MCT8. Surprisingly, accumulation of peripherally injected T4 and T3 into the kidneys was found to be enhanced in the absence of MCT8, indicating that MCT8 deficiency either directly interferes with the renal efflux of thyroid hormones or activates indirectly other renal thyroid hormone transporters that preferentially mediate the renal uptake of thyroid hormones. Our findings indicate that the enhanced uptake and accumulation of T4 in the kidneys of MCT8 null mice together with the increased renal conversion of T4 into T3 by increased renal deiodinase type 1 activities contributes to the generation of the low-serum T4 and the increase in circulating T3 levels, a hallmark of MCT8 deficiency.

Serum iodothyronine concentrations in intestinally decontaminated rats treated with a 5′-deiodinase type I inhibitor 6-anilino-2-thiouracil

1996 ◽  
Vol 134 (4) ◽  
pp. 519-523 ◽  
Author(s):  
Irini E Veronikis ◽  
Sharon Alex ◽  
Shih-Lieh Fang ◽  
George Wright ◽  
Sing-Yung Wu ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Group Treatment ◽  
Enterohepatic Circulation ◽  
Enteric Bacteria ◽  
Male Rats ◽  
Type I ◽  
Iodothyronine Deiodinase ◽  
Intestinal Decontamination ◽  
Hydrolysis Of

Veronikis IE, Alex S, Fang S-L, Wright G, Wu S-Y, Chanoine JP, Emerson CH, Braverman LE. Serum iodothyronine concentrations in intestinally decontaminated rats treated with a 5′-deiodinase type I inhibitor 6-anilino-2-thiouracil. Eur J Endocrinol 1996;134:519–23. ISSN 0804–4643 Enteric bacteria have been postulated to have a role in thyroid economy by promoting the hydrolysis of thyroid hormone conjugates of biliary origin, thus permitting the absorption and recycling of thyroxine (T4) and triiodothyronine (T3). An enterohepatic circulation of T3 might be more pronounced under conditions in which type I iodothyronine deiodinase activity (5′D-I) is inhibited, because this augments the accumulation of T3 sulfate conjugates in bile. This potential of increased gut reabsorption of T3 might explain, at least in part, the failure of serum T3 values to decrease appreciably when marked reductions in peripheral 5′D-I activity are induced by selenium deficiency or 6-anilino-2-thiouracil (ATU) administration. Thus, studies were performed to determine the effect of intestinal decontamination, in the absence and in the presence of 5′D-I inhibition, on plasma T4 and T3 concentrations. Groups of adult male rats received either enteric antibiotics or no antibiotics for 12 days and then, in half of the rats in each group, treatment for 10 days with ATU, a 5′D-I inhibitor that does not affect thyroid hormone synthesis. The activity of intestinal arylsulfatase and arylsulfotransferase, enzymes that catalyze hydrolysis of thyroid hormone conjugates, was reduced markedly by approximately 87% in rats that received antibiotics, regardless of whether or not they also received ATU. The ATU treatment markedly inhibited liver 5′D-I activity in antibiotic-treated as well as in non-antibiotic-treated rats (control = 399 ± 32 U/mg protein (mean ± sem); ATU = 152 ± 17; antibiotics = 351 ± 29; antibiotics + ATU = 130 ± 10; p < 0.01) and significantly increased plasma T4 and T3 sulfate (T4S, T3S) concentrations (control: T4S = 2.8 ± 0.4 and T3S = 6.7 ± 1.3 ng/dl; ATU: T4S = 6.2 ± 1.4 and T3S = 10.6 ± 2.1 ng/dl; antibiotics: T4S = 1.8 ± 0.2 and T3S = 3.6 ± 1.0 ng/dl; antibiotics + ATU: T4S = 6.8 ± 0.7 and T3S = 9.7 ± 1.8 ng/dl; p < 0.05). The ATU treatment was associated with a significant increase in plasma T4 and rT3 concentrations but did not affect plasma T3 concentrations, and intestinal decontamination did not alter these ATU-associated effects on circulating thyroid hormones. These results suggest that anaerobic enteric bacteria in the rat do not have an important role in recycling of thyroid hormones, either under normal conditions or in circumstances where 5′D-I activity is markedly reduced, and that increased gut absorption of T3 from T3S cannot explain the near-normal serum T3 values found when peripheral 5′D-I activity is markedly decreased. Lewis E Braverman, Endocrinology Division, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA

Insight into the physiological actions of thyroid hormone receptors from genetically modified mice

2002 ◽  
Vol 175 (3) ◽  
pp. 553-570 ◽  
Author(s):  
PJ O'Shea ◽  
GR Williams
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Genetically Modified ◽  
Receptor Protein ◽  
Mrna Isoforms ◽  
Iodothyronine Deiodinase ◽  
Thyrotrophin Releasing Hormone ◽  
Genetically Modified Mice

Thyroid hormones exert a range of developmental and physiological actions in all vertebrates. Serum concentrations of L-thyroxine (T4) and 3,5,3 -L-triiodothyronine (T3) are maintained by a negative feedback loop involving T3-inhibition of hypothalamic thyrotrophin releasing hormone (TRH) and pituitary thyroid stimulating hormone (TSH) secretion, and by tissue specific and hormone-regulated expression of the three iodothyronine deiodinase enzymes that activate or metabolise thyroid hormones. T3 actions are mediated by two T3-receptors, TRalpha and TRbeta, which act as hormone-inducible transcription factors. The TRalpha (NR1A1) and TRbeta (NR1A2) genes encode mRNAs that are alternatively spliced to generate 9 mRNA isoforms (TRalpha1, alpha2, alpha3, Deltaalpha1, Deltaalpha2, beta1, beta2, beta3 and Deltabeta3), of which four (TRalpha1, alpha2, beta1 and beta2) are known to be expressed at the protein level in vivo. The numerous TR mRNAs are expressed widely in tissue- and developmental stage-specific patterns, although it is important to note that levels of mRNA expression may not correlate with receptor protein concentrations in individual tissues. The TRalpha2, alpha3, Deltaalpha1 and Deltaalpha2 transcripts encode proteins that fail to bind T3 in vitro. These non-binding isoforms, in addition to TRDeltabeta3 which does bind hormone, may act as dominant negative antagonists of the true T3-binding receptors in vitro, but their physiological functions and those of the TRbeta3 isoform have not been determined. In order to obtain a new understanding of the complexities of T3 action in vivo and the role of TRs during development, many mouse models of disrupted or augmented thyroid hormone signalling have been generated. The aim of this review is to provide a picture of the physiological actions of thyroid hormones by considering the phenotypes of these genetically modified mice.

Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data

2021 ◽  
Vol 53 (04) ◽  
pp. 272-279
Author(s):  
Chaochao Ma ◽  
Xiaoqi Li ◽  
Lixin Liu ◽  
Xinqi Cheng ◽  
Fang Xue ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Pregnant Women ◽  
Early Pregnancy ◽  
Gestational Age ◽  
Dynamic Change ◽  
Reference Intervals ◽  
Thyroid Stimulating Hormone ◽  
Free Thyroxine ◽  
Stimulating Hormone

AbstractThyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052–3.393 μIU/ml, 1.01–1.54 ng/dl, and 2.51–3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

scholarly journals Blood Micronutrient and Thyroid Hormone Concentrations in the Oldest-Old

2000 ◽  
Vol 85 (6) ◽  
pp. 2260-2265 ◽  
Author(s):  
Giovanni Ravaglia ◽  
Paola Forti ◽  
Fabiola Maioli ◽  
Barbara Nesi ◽  
Loredana Pratelli ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Oldest Old ◽  
Serum Zinc ◽  
Blood Levels ◽  
Elderly Age ◽  
Blood Concentrations ◽  
Significant Difference ◽  
Plasma Retinol ◽  
Age Range

Several micronutrients are involved in thyroid hormone metabolism, but it is unclear whether their marginal deficits may contribute to the alterations in thyroid function observed in extreme aging. The relationships among blood concentrations of thyroid hormones and selenium, zinc, retinol, and α-tocopherol were studied in 44 healthy Northern Italian oldest-old subjects (age range, 90–107 yr), selected by the criteria of the SENIEUR protocol. Control groups included 44 healthy adult (age range, 20–65 yr) and 44 SENIEUR elderly (age range, 65–89 yr) subjects. Oldest-old subjects had higher TSH (P &lt; 0.01) and lower free T3 (FT3)/freeT4 (FT4) ratio, zinc, and selenium serum values (P &lt; 0.001) than adult and elderly control subjects. No significant difference was found for plasma retinol and α-tocopherol values. The associations between micronutrients and thyroid hormones were evaluated by multivariate analysis. In oldest-old subjects, plasma retinol was negatively associated with FT4 (P = 0.019) and TSH serum levels (P = 0.040), whereas serum zinc was positively associated with serum FT3 (P = 0.010) and FT3/FT4 ratio (P = 0.011). In younger subjects, no significant association was found among thyroid variables and micronutrients. In conclusion, blood levels of specific micronutrients are associated with serum iodothyronine levels in extreme aging.

scholarly journals PCB-Related Alteration of Thyroid Hormones and Thyroid Hormone ReceptorGene Expression in Free-Ranging Harbor Seals (Phoca vitulina)

2006 ◽  
Vol 114 (7) ◽  
pp. 1024-1031 ◽  
Author(s):  
Maki Tabuchi ◽  
Nik Veldhoen ◽  
Neil Dangerfield ◽  
Steven Jeffries ◽  
Caren C. Helbing ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Phoca Vitulina ◽  
Harbor Seals ◽  
Free Ranging
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