Thyroid hormone protects human lung epithelial cells from cold preservation and warm reperfusion-induced injury.

BACKGROUND: Cellular stress associated with static-cold storage (SCS) and warm reperfusion of donor lungs can contribute to ischemia-reperfusion (IR) injury during transplantation. Adding cytoprotective agents to the preservation solution may be conducive to reducing graft deterioration and improving post-transplant outcomes. METHODS: SCS and warm reperfusion were simulated in human lung epithelial cells (BEAS-2B) by exposing cells to low potassium dextran glucose solution at 4 °C for different periods and then switching back to serum-containing culture medium at 37 °C. Transcriptomic analysis was used to explore potential cytoprotective agents. Based on its results, cell viability, caspase activity, cell morphology, mitochondrial function, and inflammatory gene expression were examined under simulated IR conditions with or without thyroid hormones (THs). RESULTS: After 18 h SCS followed by 2 h warm reperfusion, genes related to inflammation and cell death were upregulated, and genes related to protein synthesis and metabolism were downregulated in BEAS-2B cells, which closely mirrored gene profiles found in thyroid glands of mice with congenital hypothyroidism. The addition of THs (T3 or T4) to the preservation solution increases cell viability, inhibits activation of caspase 3, 8 and 9, preserves cell morphology, enhances mitochondrial membrane potential, reduces mitochondrial superoxide production, and suppresses inflammatory gene expression. CONCLUSION: Adding THs to lung preservation solutions may protect lung cells during SCS by promoting mitochondrial function, reducing apoptosis, and inhibiting pro-inflammatory pathways. Further in vivo testing is warranted to determine the potential clinical application of adding THs as therapeutics in lung preservation solutions.

A combination of silymarin and garlic extract enhances thyroid hormone activation and body metabolism in orally intoxicated male rats with atrazine: Impact on hepatic iodothyronine deiodinase type 1.

Atrazine is a widely applied herbicide to improve crop yield and maintain general health. It has been reported to impair thyroid function and architecture in experimental animals. Alterations in thyroid hormones disrupt normal body function and metabolism. Silymarin, a hepatoprotective flavonolignan, was found to improve thyroid function and body metabolism. Additionally, garlic displays several protective effects on body organs. Therefore, this study explored the prophylactic impact of natural compounds comprising silymarin and garlic extract on disrupted thyroid function, hepatic iodothyronine deiodinase type 1, and metabolic parameters in atrazine-intoxicated male rats. We found that daily pre- and co-treatment of atrazine-intoxicated male rats with silymarin (100 mg/kg, p.o) and/or garlic extract (10 mg/kg, p.o) significantly improved thyroid activation and hepatic functionality as evidenced by the re-establishment of T3, T3/T4, and TSH values as well as ALT and AST activities. Interestingly, individual or concurrent supplementation of the atrazine group with silymarin and garlic extract prevented the down-regulation in hepatic iodothyronine deiodinase type 1. These effects were coupled with the repletion of serum and hepatic antioxidants and the amelioration of lipid peroxidation. In addition, current natural products markedly alleviated weight gain, dyslipidemia, hyperglycemia, glucose intolerance, and insulin resistance. Notably, a cocktail of silymarin and garlic extract exerted superior protection against atrazine-triggered deterioration of thyroid, hepatic, and metabolic functioning to individual treatments. Present findings pinpoint the prophylactic and synergistic influence of silymarin and garlic extract combinatorial regimen on thyroid activation and body metabolism via enhancing antioxidant potential, maintaining hepatic function, and iodothyronine deiodinase type 1.

The effects of choline supplementation in mothers with hypothyroidism on the alteration of cognitive-behavioral, long-term potentiation, morphology, and apoptosis in the hippocampus of pre-pubertal offspring rats.

The mother's thyroid hormone status during gestation and the first few months after delivery can play a crucial role in maturation during the brain development of the child. Transient abnormalities in thyroid function at birth indicate developmental and cognitive disorders in adulthood. Choline supplementation during gestation and the perinatal period in rats causes long-lasting memory improvement in the offspring. However, it remains unclear whether choline is able to restore the deficits in rats with maternal hypothyroidism. The aim of this study was to evaluate the effects of choline supplementation on the alteration of cognitive-behavioral function, long-term potentiation (LTP), and morphological changes as well as apoptosis in pre-pubertal offspring rats. To induce hypothyroidism, 6-propyl-2-thiouracil was added to the drinking water from the 6th day of gestation to the 21st postnatal day (PND). Choline treatment was started twice a day on the first day of the gestation until PND 21 via gavage. LTP recording and Morris water maze (MWM) test were conducted at PND 28. Then, the rats were sacrificed to assess their brains. The results revealed that developmental thyroid hormone deficiency impaired spatial learning and memory and reduced LTP (both: P < 0.001). Choline treatment alleviated LTP (P < 0.001), as well as learning and memory deficits (P < 0.01) in both male and female hypothyroid rats. However, no significant changes were observed in the number of caspase-3 stained cells in choline-receiving hypothyroid groups. The results revealed that developmental thyroid hormone deficiency impaired spatial learning and memory and reduced LTP. Choline treatment alleviated LTP, as well as learning and memory deficits in both male and female hypothyroid rats.

The Differential Effect of a Shortage of Thyroid Hormone Compared with Knockout of Thyroid Hormone Transporters Mct8 and Mct10 on Murine Macrophage Polarization.

Innate immune cells, including macrophages, are functionally affected by thyroid hormone (TH). Macrophages can undergo phenotypical alterations, shifting between proinflammatory (M1) and immunomodulatory (M2) profiles. Cellular TH concentrations are, among others, determined by TH transporters. To study the effect of TH and TH transporters on macrophage polarization, specific proinflammatory and immunomodulatory markers were analyzed in bone marrow-derived macrophages (BMDMs) depleted of triiodothyronine (T3) and BMDMs with a knockout (KO) of Mct8 and Mct10 and a double KO (dKO) of Mct10/Mct8. Our findings show that T3 is important for M1 polarization, while a lack of T3 stimulates M2 polarization. Mct8 KO BMDMs are unaffected in their T3 responsiveness, but exhibit slight alterations in M2 polarization, while Mct10 KO BMDMs show reduced T3 responsiveness, but unaltered polarization markers. KO of both the Mct8 and Mct10 transporters decreased T3 availability and, contrary to the T3-depleted BMDMs, showed partially increased M1 markers and unaltered M2 markers. These data suggest a role for TH transporters besides transport of TH in BMDMs. This study highlights the complex role of TH transporters in macrophages and provides a new angle on the interaction between the endocrine and immune systems.

Utilization of temperature-mediated activation of thyroid hormone-induced molecular memory to evaluate early signaling events in the olfactory epithelium of Rana [Lithobates] catesbeiana tadpoles.

The amphibian olfactory system is highly distinct between aquatic tadpole and terrestrial frog life stages and therefore must remodel extensively during thyroid hormone (TH)-dependent metamorphosis. Developmentally appropriate functioning of the olfactory epithelium is critical for survival. Previous studies in other Rana [Lithobates] catesbeiana premetamorphic tadpole tissues showed that initiation of TH-induced metamorphosis can be uncoupled from execution of TH-dependent programs by holding tadpoles in the cold rather than at warmer permissive temperatures. TH-exposed tadpoles at the nonpermissive (5 °C) temperature do not undergo metamorphosis but retain a "molecular memory" of TH exposure that is activated upon shift to a permissive warm temperature. Herein, premetamorphic tadpoles were held at permissive (24 °C) or nonpermissive (5 °C) temperatures and injected with 10 pmoles/g body weight 3,5,3'-triiodothyronine (T3) or solvent control. Olfactory epithelium was collected at 48 h post-injection. RNA-sequencing (RNA-Seq) and reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) analyses generated differentially expressed transcript profiles of 4328 and 54 contigs for permissive and nonpermissive temperatures, respectively. Translation, rRNA, spliceosome, and proteolytic processes gene ontologies were enriched by T3 treatment at 24 °C while negative regulation of cell proliferation was enriched by T3 at 5 °C. Of note, as found in other tissues, TH-induced basic leucine zipper-containing protein-encoding transcript, thibz, was significantly induced by T3 at both temperatures, suggesting a role in the establishment of molecular memory in the olfactory epithelium. The current study provides critical insights by deconstructing early TH-induced induction of postembryonic processes that may be targets for disruption by environmental contaminants.

Thyroid hormone receptor alpha modulates fibrogenesis in hepatic stellate cells.

OBJECTIVE: Progressive hepatic fibrosis can be considered the final stage of chronic liver disease. Hepatic stellate cells (HSC) play a central role in liver fibrogenesis. Thyroid hormones (TH, e.g. thyroxine; T4 and triiodothyronine; T3) significantly affect development, growth, cell differentiation and metabolism through activation of TH receptor α and/or ß (TRα/ß). Here, we evaluated the influence of TH in hepatic fibrogenesis. DESIGN: Human liver tissue was obtained from explanted livers following transplantation. TRα-deficient (TRα-KO) and wild-type (WT) mice were fed a control or a profibrogenic methionine-choline deficient (MCD) diet. Liver tissue was assessed by qRT-PCR for fibrogenic gene expression. In vitro, HSC were treated with TGFß in the presence or absence of T3. HSC with stable TRα knockdown and TRα deficient mouse embryonic fibroblasts (MEF) were used to determine receptor-specific function. Activation of HSC and MEF was assessed using the wound healing assay, Western blotting, and qRT-PCR. RESULTS: TRα and TRß expression is downregulated in the liver during hepatic fibrogenesis in humans and mice. TRα represents the dominant isoform in HSC. In vitro, T3 blunted TGFß-induced expression of fibrogenic genes in HSC and abrogated wound healing by modulating TGFß signalling, which depended on TRα presence. In vivo, TRα-KO enhanced MCD diet-induced liver fibrogenesis. CONCLUSION: These observations indicate that TH action in non-parenchymal cells is highly relevant. The interaction of TRα with TH regulates the phenotype of HSC via the TGFß signalling pathway. Thus, the TH-TR axis may be a valuable target for future therapy of liver fibrosis.

In vitro screening of per- and polyfluorinated substances (PFAS) for interference with seven thyroid hormone system targets across nine assays.

The US Environmental Protection Agency is evaluating the ecological and toxicological effects of per- and polyfluorinated chemicals. A number of perfluorinated chemicals have been shown to impact the thyroid axis in vivo suggesting that the thyroid hormone system is a target of these chemicals. The objective of this study was to evaluate the activity of 136 perfluorinated chemicals at seven key molecular initiating events (MIE) within the thyroid axis using nine in vitro assays. The potential MIE targets investigated are Human Iodothyronine Deiodinase 1 (hDIO1), Human Iodothyronine Deiodinase 2 (hDIO2), Human Iodothyronine Deiodinase 3 (hDIO3), Xenopus Iodothyronine Deiodinase (xDIO3); Human Iodotyrosine Deiodinase (hIYD), Xenopus Iodotyrosine Deiodinase (xIYD), Human Thyroid Peroxidase (hTPO); and the serum binding proteins Human Transthyretin (hTTR) and Human Thyroxine Binding Globulin (hTBG). Of the 136 PFAS chemicals tested, 85 had sufficient activity to produce a half-maximal effect concentration (EC50) in at least one of the nine assays. In general, most of these PFAS chemicals did not have strong potency towards the seven MIEs examined, apart from transthyretin binding, for which several PFAS had potency similar to the respective model inhibitor. These data sets identify potentially active PFAS chemicals to prioritize for further testing in orthogonal in vitro assays and at higher levels of biological organization to evaluate their capacity for altering the thyroid hormone system and causing potential adverse health and ecological effects.

[Disruptors of thyroid hormones: Which consequences for human health and environment?] / Les perturbateurs des hormones thyroïdiennes : comment estimer leurs impacts sur la santé humaine et l'environnement ?

Endocrine disruptors (EDs) of chemical origin are the subject of numerous studies, some of which have led to measures aimed at limiting their use and their impact on the environment and human health. Dozens of hormones have been described and are common to all vertebrates (some chemically related messengers have also been identified in invertebrates), with variable roles that are not always known. The effects of endocrine disruptors therefore potentially concern all animal species via all endocrine axes. These effects are added to the other parameters of the exposome, leading to strong, multiple and complex adaptive pressures. The effects of EDs on reproductive and thyroid pathways have been among the most extensively studied over the last 30 years, in a large number of species. The study of the effects of EDs on thyroid pathways and brain development goes hand in hand with increasing knowledge of 1) the different roles of thyroid hormones at cellular or tissue level (particularly developing brain tissue) in many species, 2) other hormonal pathways and 3) epigenetic interactions. If we want to understand how EDs affect living organisms, we need to integrate results from complementary scientific fields within an integrated, multi-model approach (the so-called translational approach). In the present review article, we aim at reporting recent discoveries and discuss prospects for action in the fields of medicine and research. We also want to highlight the need for an integrated, multi-disciplinary approach to studying impacts and taking appropriate action.

Title: Les perturbateurs des hormones thyroïdiennes : comment estimer leurs impacts sur la santé humaine et l'environnement ? Abstract: Les perturbateurs endocriniens (PE) d'origine chimique font l'objet de nombreuses études, certaines ayant permis des mesures visant à limiter leur utilisation et leurs impacts sur l'environnement et la santé humaine. Des dizaines d'hormones ont été décrites et sont communes à l'ensemble des vertébrés (certains messagers chimiquement proches ont été également répertoriés chez les invertébrés) avec des rôles variables et pas toujours connus. Les effets des PE concernent donc potentiellement toutes les espèces animales via tous les axes endocriniens ; ils s'ajoutent aux autres paramètres de l'exposome qui induisent une pression d'adaptation forte, multiple, et difficile à appréhender. Les effets des PE sur les voies de la reproduction et les voies thyroïdiennes sont parmi les plus étudiés depuis ces trente dernières années et ce, sur un grand nombre d'espèces. L'étude des effets des PE sur les voies thyroïdiennes ainsi que sur le développement cérébral va de pair avec l'augmentation des connaissances sur 1) les différents rôles des hormones thyroïdiennes au niveau cellulaire ou tissulaire (notamment le tissu cérébral en développement) chez de nombreuses espèces, 2) les autres voies hormonales et 3) les interactions épigénétiques. De façon générale, si l'on veut appréhender comment agissent les PE sur les organismes vivants, il est nécessaire d'analyser dans une approche intégrée et multi-modèles (approche dite translationnelle) les résultats issus de domaines scientifiques complémentaires. Dans cette brève revue, nous dressons un état des lieux de découvertes récentes et discutons les perspectives d'action dans les champs de la médecine et de la recherche. Nous mettons en avant la nécessité d'une approche intégrée et multidisciplinaire pour étudier les impacts des PE et prendre des mesures appropriées.

TSH Pulses Finely Tune Thyroid Hormone Release and TSH Receptor Transduction.

Detection of circulating TSH is a first-line test of thyroid dysfunction, a major health problem (affecting about 5% of the population) that, if untreated, can lead to a significant deterioration of quality of life and adverse effects on multiple organ systems. Human TSH levels display both pulsatile and (nonpulsatile) basal TSH secretion patterns; however, the importance of these in regulating thyroid function and their decoding by the thyroid is unknown. Here, we developed a novel ultra-sensitive ELISA that allows precise detection of TSH secretion patterns with minute resolution in mouse models of health and disease. We characterized the patterns of ultradian TSH pulses in healthy, freely behaving mice over the day-night cycle. Challenge of the thyroid axis with primary hypothyroidism because of iodine deficiency, a major cause of thyroid dysfunction worldwide, results in alterations of TSH pulsatility. Induction in mouse models of sequential TSH pulses that mimic ultradian TSH profiles in periods of minutes were more efficient than sustained rises in basal TSH levels at increasing both thyroid follicle cAMP levels, as monitored with a genetically encoded cAMP sensor, and circulating thyroid hormone. Hence, this mouse TSH assay provides a powerful tool to decipher how ultradian TSH pulses encode thyroid outcomes and to uncover hidden parameters in the TSH-thyroid hormone set-point in health and disease.

Bisphenol S dysregulates thyroid hormone homeostasis; Testicular survival, redox and metabolic status: Ameliorative actions of melatonin.

Bisphenol S (BPS) is an incipient threat for reproductive health augmenting societal burden of infertility worldwide. In the present study, we investigated the mechanism of BPS induced testicular dysfunctions and protective actions of melatonin in mice. BPS (150 mg/kg BW) treatment reduced serum T3/T4, testosterone and elevated insulin levels along with adverse effect on thyroid and testicular histoarchitecture. Further, BPS treatment compromised sperm quality, reduced mRNA expression of steroidogenic (StAR/CYP11A1) markers, elevated oxidative load and disrupts metabolic status. However, melatonin (5 mg/kg BW) administration to BPS treated mice showed improved hormonal/histological parameters, enhanced thyroid hormone (TR-α/Dio-2)/melatonin (MT-1) receptor expressions. Further, melatonin treatment modulated the expression of testicular survival/redox (SIRT1/PGC-1α/FOXO-1, Nrf2/HO-1, p-JAK2/p-STAT3), proliferative (PCNA) and metabolic (IR/pAKT/GLUT-1) markers. Furthermore, melatonin treatment enhanced testicular antioxidant status and reduced caspase-3 expression. In conclusion, our results showed that BPS induces endocrine/oxidative and metabolic anomalies while melatonin improved male reproductive health.

Prospective Effect of Nano-Selenium Particles on Thyroid Dysfunction and Oxidative Stress Induced by Sodium Benzoate in Male Albino Rats.

&lt;b&gt;Background and Objective:&lt;/b&gt; The negative effects of preservatives, such as sodium benzoate, have received increasing global attention. The objective of the study was to investigate the potential protective effects of nano-selenium (nano-Se) on thyroid functions, oxidative stress and inflammatory cytokine responses of albino rats. &lt;b&gt;Materials and Methods:&lt;/b&gt; Thirty-five male rats were divided into five groups, 7 rats in each: GI: A control group, GII: Corn oil, GIII: Nano-selenium, GIV: Sodium benzoate, GV: Selenium nanoparticles followed with sodium benzoate. At the end of study, sera were separated from all rats for estimation of MDA, GSH, GSH-PX, glucose, interleukin-1ß, TSH, T3, FT3, T4 and FT4. All data were statistically analyzed using Analysis of Variance (ANOVA). &lt;b&gt;Results:&lt;/b&gt; Sodium benzoate treatment showed opposite effects as it decreased levels of T3, FT3, F4, FT4, GSH and GSH-PX. On the contrary, it increased serum levels of TSH, MDA, NO, glucose and IL-1β when compared to the control group. Whereas, nano-selenium promoted a significant increase in levels of thyroid hormones T3, T4 and FT4, upgrading GSH and GSH-PX. While it reduced TSH, MDA, NO, glucose and IL-1β levels when compared to the sodium benzoate group. &lt;b&gt;Conclusion:&lt;/b&gt; Nano-selenium treatment as a protector showed the ability to reduce lipid peroxidation and restore glutathione peroxidase activity, thus, selenium complex at nano-level can reduce oxidative stress and damage of thyroid hormones caused by sodium benzoate administration.

Plasticity of cone photoreceptors in adult zebrafish revealed by thyroid hormone exposure.

Vertebrate color vision is predominantly mediated by the presence of multiple cone photoreceptor subtypes that are each maximally sensitive to different wavelengths of light. Thyroid hormone (TH) has been shown to be essential in the spatiotemporal patterning of cone subtypes in many species, including cone subtypes that express opsins that are encoded by tandemly replicated genes. TH has been shown to differentially regulate the tandemly replicated lws opsin genes in zebrafish, and exogenous treatments alter the expression levels of these genes in larvae and juveniles. In this study, we sought to determine whether gene expression in cone photoreceptors remains plastic to TH treatment in adults. We used a transgenic lws reporter line, multiplexed fluorescence hybridization chain reaction in situ hybridization, and qPCR to examine the extent to which cone gene expression can be altered by TH in adults. Our studies revealed that opsin gene expression, and the expression of other photoreceptor genes, remains plastic to TH treatment in adult zebrafish. In addition to retinal plasticity, exogenous TH treatment alters skin pigmentation patterns in adult zebrafish after 5 days. Taken together, our results show a remarkable level of TH-sensitive plasticity in the adult zebrafish.

Nutrigenómica y funcionamiento de las hormonas tiroideas, un efecto dependiente de la ingesta materna de fructosa / Nutrigenomics and thyroid hormone functioning, a dependent effect of maternal fructose intake

El consumo de fructosa se ha asociado con el desarrollo de síndrome metabólico. También se ha demostrado que la ingesta de fructosa durante la gestación puede provocar efectos perjudiciales en los descendientes (1). Además, otros autores han descrito cómo la nutrición puede afectar al funcionamiento de las hormonas tiroideas, las cuales están implicadas en diversas enfermedades metabólicas.Por ello, se determinaron el efecto del consumo materno de fructosa durante la gestación sobre el metabolismo de las hormonas tiroideas en sus descendientes, y los efectos de la suplementación de los descendientes con distintas dietas (fructosa, tagatosa, fructosa con colesterol).La tagatosa aumentó los niveles plasmáticos de T4 libre y la expresión hepática de DIO1 solamente en descendientes de madres fructosa. Sin embargo, la expresión hepática de UCP2 mostró un perfil más similar a la de THRa.En íleon y TAL los perfiles de expresión para DIO1 y UCP están correlacionados y se ven afectados por el consumo de fructosa (efecto dependiente de la ingesta materna). La adición de colesterol a la dieta potenció el efecto de la fructosa en íleon (para DIO1 y UCP2).Por tanto, el consumo materno de fructosa afecta al metabolismo de las hormonas tiroideas de la descendencia, tanto en respuesta a una dieta rica en fructosa como a la asociación de fructosa y colesterol (“Western diet”).Este trabajo pretende alertar a la población, en especial mujeres embarazadas del papel relevante que ejerce la nutrición, con posibles consecuencias negativas para la salud de sus hijos.(AU)

Fructose consumption has been associated with the development of metabolic syndrome. It has also been shown that fructose intake during pregnancy can cause detrimental effects on offspring (1). In addition, other authors have described how nutrition can affect the function of thyroid hormones, which are involved in various metabolic diseases.Therefore, we determined the effect of maternal fructose consumption during pregnancy on the metabolism of thyroid hormones in their offspring and the effects of the supplementation with different diets (fructose, tagatose, fructose with cholesterol) in the offspring.Tagatose increased plasma free T4 levels and hepatic DIO1 expression only in the offspring of fructose-fed mothers. However, the hepatic expression of UCP2 showed a profile more similar to that of THRa.In ileum and TAL, the expression profiles for DIO1 and UCP are correlated and affected by fructose consumption (effect dependent on maternal intake). The addition of cholesterol to the diet potentiated the effect of fructose in ileum (for DIO1 and UCP2).Thus, maternal fructose consumption affects the metabolism of thyroid hormones in the offspring, both in response to a fructose rich diet and a combination of fructose and cholesterol (“Western diet”).This work aims to alert the population, especially pregnant women, of the relevant role of nutrition, leading to possible negative consequences for the health of their children.(AU)

Analysis of evolutionary and functional features of the bullfrog SULT1 family.

We identified the bullfrog Rana catesbeiana sulfotransferase 1 (SULT1) family from the BLAST search tool of the public databases based on the SULT1 families of Nanorana parkeri, Xenopus laevis, and Xenopus tropicalis as queries, revealing the characteristics of the anuran SULT1 family. The results showed that the anuran SULT1 family comprises six subfamilies, four of which were related to the mammalian SULT1 subfamily. Additionally, the bullfrog has two SULT1Cc subfamily members that are consistent with the characteristics of the expanded Xenopus SULT1C subfamily. Several members of the bullfrog SULT1 family were suggested to play important roles in sulfation during metamorphosis. Among these, cDNAs encoding SULT1Cc1 and SULT1Y1 were cloned, and the sulfation activity was analyzed using recombinant proteins. The affinity for 2-naphthol and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and the enzymatic reaction rate were higher in SULT1Cc1 than in SULT1Y1. Both the enzymes showed inhibitory effect of many thyroid hormones (THs) analogs on the sulfation of 2-naphthol. The potency of sulfation activities of SULT1Cc1 and SULT1Y1 against T4 indicated their possible role in the intracellular T4 clearance during metamorphosis.

Environmentally relevant concentrations of triclosan induce lethality and disrupt thyroid hormone activity in zebrafish (Danio rerio).

Triclosan is an antimicrobial agent that has been used in common household products and can be detected in water environment. In this study, therefore, I aimed at clarifying the effects of environmentally relevant concentrations of triclosan on the early life stage development in zebrafish. A lethal effect was observed: the lowest effect and the no effect concentrations were 70.6 and 48.4 µg/L, respectively. These concentrations are very close to the environmentally detected residual concentrations. In 10.9, 19.8, 48.4, and 70.6 µg/L of triclosan, the iodothyronine deiodinase 1 gene expression was found to be significantly increased when compared with that of the control group. These findings indicate that triclosan can potentially disrupt the thyroid hormone activity in zebrafish. The exposure to triclosan (at 149.2 µg/L) was also found to inhibit the gene expression of insulin-like growth factor-1. My findings suggest that triclosan can exert a thyroid hormone-disrupting effect on fish.

A biologically based computational model for the hypothalamic-pituitary-thyroid (HPT) axis in Xenopus laevis larvae.

A biologically based computational model was developed to describe the hypothalamic-pituitary-thyroid (HPT) axis in developing Xenopus laevis larvae. The goal of this effort was to develop a tool that can be used to better understand mechanisms of thyroid hormone-mediated metamorphosis in X. laevis and predict organismal outcomes when those mechanisms are perturbed by chemical toxicants. In this report, we describe efforts to simulate the normal biology of control organisms. The structure of the model borrows from established models of HPT axis function in mammals. Additional features specific to X. laevis account for the effects of organism growth, growth of the thyroid gland, and developmental changes in regulation of thyroid stimulating hormone (TSH) by circulating thyroid hormones (THs). Calibration was achieved by simulating observed changes in stored and circulating levels of THs during a critical developmental window (Nieuwkoop and Faber stages 54-57) that encompasses widely used in vivo chemical testing protocols. The resulting model predicts that multiple homeostatic processes, operating in concert, can act to preserve circulating levels of THs despite profound impairments in TH synthesis. Represented in the model are several biochemical processes for which there are high-throughput in vitro chemical screening assays. By linking the HPT axis model to a toxicokinetic model of chemical uptake and distribution, it may be possible to use this in vitro effects information to predict chemical effects in X. laevis larvae resulting from defined chemical exposures.

Glucagon-modified Liposomes Delivering Thyroid Hormone for Anti-obesity Therapy.

BACKGROUND: Thyroid hormones (active form T3) are naturally potent compounds that influence energy expenditure, cholesterol metabolism, and fat oxidation. T3 would be an effective anti-obesity drug if it would not be delivered to the heart and bones, which leads to serious side effects, such as cardiovascular and bone thyrotoxicity, muscle wasting, and so on. METHODS: In this study, we designed a targeted drug delivery system that is a glucagon-modified liposome to deliver T3 to the liver and adipose tissues. RESULTS: The liposomes exhibited excellent properties, including uniform nanoscale particle size, good physicochemical stability, and adequate drug release behavior. More importantly, the glucagon-modified liposomes were enriched in the liver, which minimized the undesired bone and cardiovascular thyrotoxicity of T3. Compared to the control group, T3-loading glucagon-modified liposomes could effectively decrease body weight, reverse hepatic steatosis, and correct hyperlipidemia and hyperglycemia in ob/ob mice, without the undesired cardiovascular and bone thyrotoxicity. CONCLUSION: These findings indicate that delivery of thyroid hormone by glucagon-modified liposomes may provide an effective strategy for anti-obesity therapy.

Effects of intracerebroventricular MOTS-c infusion on thyroid hormones and uncoupling proteins.

This study was conducted to determine the possible effects of intracerebroventricular MOTS-c infusion on thyroid hormones and uncoupling proteins (UCPs) in rats. Forty male Wistar Albino rats were divided into 4 groups with 10 animals in each group: control, sham, 10 and 100 µM MOTS-c. Hypothalamus, blood, muscle, adipose tissues samples were collected for thyrotropin-releasing hormone (TRH), UCP1 and UCP3 levels were determined by the RT-PCR and western blot analysis. Serum thyroid hormone levels were determined by the ELISA assays. MOTS-c infusion was found to increase food consumption but it did not cause any changes in the body weight. MOTS-c decreased serum TSH, T3, and T4 hormone levels. On the other hand, it was also found that MOTS-c administration increased UCP1 and UCP3 levels in peripheral tissues. The findings obtained in the study show that central MOTS-c infusion is a directly effective agent in energy metabolism.

Thyroid-Friendly Soft Materials as 3D Cell Culture Tool for Stimulating Thyroid Cell Function.

The disruption of thyroid hormones because of chemical exposure is a significant societal problem. Chemical evaluations of environmental and human health risks are conventionally based on animal experiments. However, owing to recent breakthroughs in biotechnology, the potential toxicity of chemicals can now be evaluated using 3D cell cultures. In this study, the interactive effects of thyroid-friendly soft (TS) microspheres on thyroid cell aggregates are elucidated and their potential as a reliable toxicity assessment tool is evaluated. Using state-of-the-art characterization methods coupled with cell-based analysis and quadrupole time-of-flight mass spectrometry, it is shown that TS-microsphere-integrated thyroid cell aggregates exhibit improved thyroid function. Specifically, the responses of zebrafish embryos, which are used for thyroid toxicity analysis, and the TS-microsphere-integrated cell aggregates to methimazole (MMI), a known thyroid inhibitor, are compared. The results show that the thyroid hormone disruption response of the TS-microsphere-integrated thyroid cell aggregates to MMI is more sensitive compared with those of the zebrafish embryos and conventionally formed cell aggregates. This proof-of-concept approach can be used to control cellular function in the desired direction and hence evaluate thyroid function. Thus, the proposed TS-microsphere-integrated cell aggregates may yield new fundamental insights for advancing in vitro cell-based research.

Hematology profile, digestive enzymes, thyroid hormones, productivity, and nitrogen balance of growing male rabbits supplemented with exogenous dietary lysozyme.

In a simple randomized design trial, 420 growing male V-Line rabbits were randomly distributed into four groups to investigate the impact of exogenous dietary lysozyme on some physiological and nutritional parameters of male growing rabbits supplemented with exogenous dietary lysozyme. The witness group received a basal diet without exogenous dietary lysozyme (LYZ0), while the exogenous dietary lysozyme groups received 50, 100 and 150 mg/kg of basal diet (Groups; LYZ50, LYZ100 and LYZ150), respectively. The results showed significantly increased in blood cell count, hemoglobin concentration, total white blood cell, lipase, protease, amylase, total protein, triiodothyronine and thyroxine levels, while thyroid stimulating hormone levels significantly lessened in rabbits received LYZ. The LYZ- rabbit diets improved total digestible nutrient, digestible crude protein, and digestible energy values, with the LYZ100 group outperforming the others. LYZ-treated rabbits had significantly higher nitrogen intake, digestible nitrogen, and nitrogen balance than the witness group. The lysozyme in a rabbit's diet is taking on a new role as a digestive enzyme, enhancement thyroid hormones, as well as improvement hematology, daily protein efficiency ratio, daily performance index, hot carcass, total edible parts, nutritional value, and nitrogen balance, with decreasing the daily caloric conversion ratio and total non-edible parts.