Hypothalamic-pituitary-thyroid Research Articles

Effect of Acute Exposure to the Ionic Liquid 1-Methyl-3-octylimidazolium Chloride on the Embryonic Development and Larval Thyroid System of Zebrafish.

Simple SummaryIn this study, we aimed to evaluate the effect of acute exposure to the ionic liquid 1-methyl-3-octylimidazolium chloride on the embryonic development and larval thyroid system of zebrafish. The results showed that the fish embryonic development, thyroid hormone level, and expression of HPTs-related genes were altered, suggesting that the ionic liquid [C8mim]Cl might pose an aquatic environmental threat to fish.Previous studies have shown that ILs can induce toxicity in animals, plants, and cells. However, the effect of imidazolium-based ILs on the hypothalamus–pituitary–thyroid (HPT) axis of fish remains unknown. The present study aimed to evaluate the acute effect of [C8mim]Cl on the embryonic development and thyroid-controlled internal secretion system of zebrafish by determining the thyroid hormone level and the expression of HPT-related genes. The results obtained for embryonic developmental toxicity showed the survival rate, heart beats, and body length of fish had decreased 96 h after exposure to [C8mim]Cl, but the hatching rate had increased by the 48 h time point. The transcription levels of HTP-related genes showed that the genes dio3, tg, ttr, tsh, trhrα, trhrβ, trhr2, and tpo were up-regulated, while the expression levels of dio1, trh, tshr, and nis were significantly suppressed. Furthermore, we found that exposure to [C8mim]Cl induced an alteration in the levels of thyroid hormones that increased the T3 but decreased the T4 content. In conclusion, our study indicated that acute exposure to [C8mim]Cl altered the expression of HTP-related genes and disturbed the thyroid hormone level, suggesting that the ionic liquid [C8mim]Cl might pose an aquatic environmental threat to fish.

Short-Term Exposure Effects of the Environmental Endocrine Disruptor Benzo(a)Pyrene on Thyroid Axis Function in Zebrafish.

Benzo(a)Pyrene (BaP) is one of the most widespread polycyclic aromatic hydrocarbons (PAHs) with endocrine disrupting properties and carcinogenic effects. In the present study, we tested the effect of BaP on thyroid development and function, using zebrafish as a model system. Zebrafish embryos were treated with 50 nM BaP from 2.5 to 72 h post fertilization (hpf) and compared to 1.2% DMSO controls. The expression profiles of markers of thyroid primordium specification, thyroid hormone (TH) synthesis, hypothalamus-pituitary-thyroid (HPT) axis, TH transport and metabolism, and TH action were analyzed in pools of treated and control embryos at different developmental stages. BaP treatment did not affect early markers of thyroid differentiation but resulted in a significant decrease of markers of TH synthesis (tg and nis) likely secondary to defective expression of the central stimulatory hormones of thyroid axis (trh, tshba) and of TH metabolism (dio2). Consequently, immunofluorescence of BaP treated larvae showed a low number of follicles immunoreactive to T4. In conclusion, our results revealed that the short-term exposure to BaP significantly affects thyroid function in zebrafish, but the primary toxic effects would be exerted at the hypothalamic-pituitary level thus creating a model of central hypothyroidism.

Insights into the Endocrine Disrupting Activity of Emerging Non-Phthalate Alternate Plasticizers against Thyroid Hormone Receptor: A Structural Perspective.

Many endocrine-disrupting chemicals (EDCs) have a ubiquitous presence in our environment due to anthropogenic activity. These EDCs can disrupt hormone signaling in the human and animal body systems including the very important hypothalamic-pituitary-thyroid (HPT) axis causing adverse health effects. Thyroxine (T4) and triiodothyronine (T3) are hormones of the HPT axis which are essential for regulation of metabolism, heart rate, body temperature, growth, development, etc. In this study, potential endocrine-disrupting activity of the most common phthalate plasticizer, DEHP, and emerging non-phthalate alternate plasticizers, DINCH, ATBC, and DEHA against thyroid hormone receptor (TRα) were characterized. The structural binding characterization of indicated ligands was performed against the TRα ligand binding site employing Schrodinger’s induced fit docking (IFD) approach. The molecular simulations of interactions of the ligands against the residues lining a TRα binding pocket, including bonding interactions, binding energy, docking score, and IFD score were analyzed. In addition, the structural binding characterization of TRα native ligand, T3, was also done for comparative analysis. The results revealed that all ligands were placed stably in the TRα ligand-binding pocket. The binding energy values were highest for DINCH, followed by ATBC, and were higher than the values estimated for TRα native ligand, T3, whereas the values for DEHA and DEHP were similar and comparable to that of T3. This study suggested that all the indicated plasticizers have the potential for thyroid hormone disruption with two alternate plasticizers, DINCH and ATBC, exhibiting higher potential for thyroid dysfunction compared to DEHA and DEHP.

IPPD-induced growth inhibition and its mechanism in zebrafish

N-isopropyl-N-phenyl-1,4-phenylenediamine (IPPD) is used as a ubiquitous antioxidant worldwide, it is an additive in tire rubber easily discharged into the surrounding environment. At present, there is no study concerning the subacute toxicity of IPPD on fish. We used zebrafish embryos (2 h post-fertilization) exposed to IPPD for 5 days at concentrations of 0, 0.0012, 0.0120 and 0.1200 mg/L to investigate its toxic effects of embryonic development, disruption of growth hormone/insulin-like growth factor (GH/IGF) and hypothalamic-pituitary-thyroid (HPT) axis. The results showed that IPPD exposure decreased hatchability, weakened movement ability, reduced body length, and caused multiple types of deformities in zebrafish embryos. The expression of genes involved to GH/IGF and HPT axis were altered after exposure to IPPD in zebrafish larvae. Meanwhile, exposure to IPPD significantly decreased thyroxine (T4) and 3,5,3′-triiodothyronine (T3) contents in larvae, which indicated that HPT axis was in a disturbed state. Moreover, treatment of IPPD decreased the enzymatic activities of superoxide dismutase (SOD) and catalase (CAT) as well as levels of glutathione (GSH). While the contents of malondialdehyde (MDA) were elevated after exposure to IPPD. The present study thus demonstrated that IPPD induced oxidative stress, caused developmental toxicity and disrupted the GH/IGF and HPT axis of zebrafish, which could be responsible for developmental impairment and growth inhibition.

Thyroid and Corticosteroid Signaling in Amphibian Metamorphosis.

In multicellular organisms, development is based in part on the integration of communication systems. Two neuroendocrine axes, the hypothalamic–pituitary–thyroid and the hypothalamic–pituitary–adrenal/interrenal axes, are central players in orchestrating body morphogenesis. In all vertebrates, the hypothalamic–pituitary–thyroid axis controls thyroid hormone production and release, whereas the hypothalamic–pituitary–adrenal/interrenal axis regulates the production and release of corticosteroids. One of the most salient effects of thyroid hormones and corticosteroids in post-embryonic developmental processes is their critical role in metamorphosis in anuran amphibians. Metamorphosis involves modifications to the morphological and biochemical characteristics of all larval tissues to enable the transition from one life stage to the next life stage that coincides with an ecological niche switch. This transition in amphibians is an example of a widespread phenomenon among vertebrates, where thyroid hormones and corticosteroids coordinate a post-embryonic developmental transition. The review addresses the functions and interactions of thyroid hormone and corticosteroid signaling in amphibian development (metamorphosis) as well as the developmental roles of these two pathways in vertebrate evolution.

Dopamine Function and Hypothalamic-Pituitary-Thyroid Axis Activity in Major Depressed Patients with Suicidal Behavior.

Involvement of the dopaminergic (DA) and hypothalamic-pituitary-thyroid (HPT) systems in suicidal behavior is still poorly understood. We assessed multihormonal responses to apomorphine (APO; a short acting DA receptor agonist) and 8 AM and 11 PM protirelin (TRH) tests in 30 medication-free DSM-5 euthyroid major depressed inpatients with suicidal behavior disorder (SBD) (current, n = 14; in early remission, n = 16) and 18 healthy hospitalized control subjects (HCs). Compared to HCs, responses to APO and TRH tests were unaltered in SBDs in early remission. However, current SBDs exhibited increased APO-induced growth hormone (GH) and adrenocorticotropin (ACTH) stimulation, and reduced 11 PM thyrotropin (TSH) and ∆∆TSH values (difference between 11 PM and 8 AM TRH-TSH responses). In current SBDs, the association between high APO-GH concentrations and low ∆∆TSH values was more common in recent suicide attempters than in past suicide attempters. These preliminary results suggest that co-occurring alterations in the DA and HPT systems (i.e., DA receptor hyperresponsiveness associated with decreased hypothalamic TRH drive) may contribute to the pathophysiology of suicidal behavior. Conversely, normalization of DA and TRH functions might reflect a process of recovery from suicidality. Thus, our findings suggest that drugs targeting the DAergic and TRH systems could be relevant in suicide prevention.

HPT‐ Axis Activation During Cold Head Out Water Immersion is Not Modified by Moderate Hypoxia

PurposeThe Bajau, an indigenous population renowned for breath‐hold diving, have comparatively large spleen volumes. This adaptation is purportedly indicative of a greater capacity to store red blood cells, which may aid operations in the aquatic environment. Spleen size in the Bajau is associated with the PDE10A genotype that encodes an enzyme that catalyzes the release of thyroxine (T4) from the thyroid gland. T4 is readily released during cold stress as the terminus to activation of the hypothalamus‐pituitary‐thyroid (HPT) ‐axis to increase metabolic rate. T4, and downstream counterpart triiodothyronine (T3), can also stimulate erythropoiesis by increasing erythropoietin production, which can be further promoted with hypoxia. Thus, exposure to cold water may augment erythropoiesis as hypoxia develops during breath‐hold diving via activation of the HPT‐axis. However, interactions between cold exposure and hypoxia on HPT‐axis activation have not been directly explored. Mountaineering expedition studies indirectly suggest that T4 release is elevated by hypoxia. Thus, this study tested the hypothesis that during cold head out water immersion (HOWI) acute hypoxia augments circulating thyroid hormone concentrations compared to normoxia.MethodsIn a randomized crossover single blind design, 12 healthy adults (27 ± 2 y, 2 women) completed one hour of cold (22.0 ± 0.1⁰C) HOWI breathing either normobaric normoxia (FiO2 = 0.21 ± 00, NORM) or normobaric hypoxia (FiO2 = 0.13 ± 00, HYP). Free (f) and total (t) T3 and T4, and thyroid stimulating hormone (TSH) were measured in venous blood samples obtained before (baseline), during (15‐, 30‐, and 60‐min), and 15 min following immersion (post‐). Arterial oxyhemoglobin saturation (SpO2) and rectal temperature were measured continuously. Data are presented as mean ± SD.ResultsSpO2 was lower in HYP (90 ± 3%) compared to NORM (98 ± 1%, p <.001). Rectal temperature did not differ between HYP and NORM (p > .711) but decreased over time in both trials (HYP ‐ baseline: 37.2 ± 0.4⁰C, post‐: 36.4 ± 0.5⁰C, p<.001, NORM ‐ baseline: 37.2 ± 0.4⁰C, post‐: 36.3 ± 0.5⁰C, p <.001). From baseline to post‐HOWI, fT3 (HYP: +0.3 ± 0.4 pg/mL, NORM: +0.4 ± 0.6 pg/mL, p <.001), fT4 (HYP: +1.6 ± 1.7 pg/mL, NORM: +0.7 ± 1.3 pg/mL, p <.001), tT3 (HYP: +0.3 ± 0.5 ng/mL, NORM: +0.2 ± 0.4 ng/mL, p= .053), and tT4 (HYP: +0.6 ± 0.4 µg%, NORM: +0.4 ± 0.5 µg%, p < .001) increased, but the magnitude did not differ between inspirates (p > .165). Relative to baseline, tT4 at 15 min (HYP: ‐0.2 ± 0.3 µg%, NORM: ‐0.3 ± 0.3 µg%, p = .025), and TSH at 30 min (HYP: ‐0.2 ± 0.2 µIU/mL, NORM: ‐0.2 ± 0.3 µIU/mL, p = .029) and 60 min (HYP: ‐0.2 ± 0.2 µIU/mL, NORM: ‐0.3 ± 0.4 µIU/mL, p = .008) of HOWI were lower, but did not differ between inspirates (p = .921).ConclusionsIncreases in circulating thyroid hormone concentrations during one hour of cold HOWI are not modified by normobaric hypoxia. Thus, moderate hypoxia does not likely affect activation of the HPT‐axis during short duration cold exposure. Further investigation is warranted to determine the possibility of circulating thyroid hormones to augment the erythropoietic response to acute hypoxia during cold exposure.

Molecular vital signs: wearable technologies for the real-time measurement of molecular markers of health and human performance

Introduction: Warfighters operate in complex and chaotic multi-stressor environments. Soldier interface with the external world on the battlefield impacts health and performance and is reflected through changes in internal physiology. Previous studies of operational stress using either cross-sectional or repeated measures designs have demonstrated substantial alterations in physiology including heightened hypothalamic-pituitary-adrenal axis (HPA) arousal, suppressed function of hypogonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) axes, and increased immune system activation1. Responses of these systems are monitored and measured via biological analytes including, but not limited to, epinephrine, norepinephrine, adrenocorticotrophic hormone, cortisol, insulin-like growth factor-I, testosterone, thyroid hormones, and inflammatory cytokines2. However, interpretation of these results is complicated by pre-analytical factors such as collection timing, sample processing, nutrient intake, and hydration status. Therefore, we propose the implementation of continuous or real-time monitoring of biological fluids (e.g., saliva, blood, sweat) for actionable information regarding hydration, muscle status, inflammation, injury risk, and metabolic health that can be used for individualized recommendations and performance optimization. Application platforms and monitoring technologies for active and passive data collection have evolved to the point where holistic surveillance is becoming feasible. For example, continuous monitoring of hormones related to systemic anabolic/catabolic balance and inflammation can help enhance physical performance and minimize overtraining, respectively3,4. Future directions: Real-time, high-fidelity tracking of biomarkers across multiple biocompartments for the purposes of enhancing health, performance, and career longevity is a next critical step for optimizing soldier readiness, lethality, and survivability in combat. Future technologies will likely enable a wider range and more precise tracking of systemic signalling (e.g., multi-omics), leading to actionable information, at the individual level, for military leaders to use in training and combat. Soldier self-report input, however, will likely remain an important aspect for guiding practices. Real-time tracking may also reorient our perception of what is deemed most physiologically relevant for monitoring soldier performance. References 1Henning PC, Park B-S, Kim J-S. Physiological decrements during sustained military operational stress. Mil Med 2011; 176:991-997. https://doi.org/10.7205/MILMED-D-11-00053 2Lee EC, Fragala MS, Kavouras SA, et al. Biomarkers in sports and exercise: tracking health, performance, and recovery in athletes. J Strength Cond Res 2017; 31:2920-2937. https://doi.org/10.1519/JSC.0000000000002122 3Kraemer WJ, Ratamess NA, Nindl BC. Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise. J App Physiol 2017; 122:549-558. https://doi.org/10.1152/japplphysiol.00599.2016 4Smith LL. Cytokine hypothesis of overtraining: a physiological adaptation to excessive stress? Med Sci Sports Exerc 2000; 32:317-331.

P290. Effect of Repetitive Transcranial Magnetic Stimulation on Chronobiological Hypothalamic-Pituitary-Thyroid Axis Activity in Major Depression

We previously demonstrated that the difference between 11 PM and 8 AM TSH response to protirelin (TRH) tests on the same day (ΔΔTSH test) is an improved measure in detecting hypothalamic-pituitary-thyroid (HPT) axis dysregulation in depression. This chronobiological index is normalized after successful antidepressant treatment. The present study aimed at assessing the effects repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) on the HPT axis activity in treatment resistant depressed inpatients (TRDs).

Exposure to enrofloxacin and depuration: Endocrine disrupting effect in juvenile grass carp (Ctenopharyngodon idella)

This study aimed to determine the effects of Enrofloxacin (ENR) exposure and depuration on the disruption of thyroid function and growth of juvenile grass carp (Ctenopharyngodon idella) as well as to assess the risk of ENR exposure to human health. Juvenile grass carp were treated with ENR solutions at different concentration gradients for 21 days and then depurated for 14 days. The results indicated ENR accumulation in the juvenile grass carp muscles, which persisted after depuration. In addition, exposure to ENR could alter growth by regulating the expression of genes associated with growth hormone/insulin-like growth factor (GH)/IGF) axis and the hypothalamic–pituitary–thyroid (HPT) axis. During ENR exposure, no significant changes in growth hormone levels were observed; however, a significant increase in the growth hormone level was noted. GH/IGF axis-related genes were upregulated after ENR exposure, and their expression levels remained high after depuration. Notably, a significant increase in the serum triiodothyronine (T3) and thyroxine (T4) levels coincided with the upregulation of HPT axis-related genes in both exposure and depuration treatments, and their expression levels remained high after depuration. Therefore, juvenile grass carp exposure to ENR induces physiological stress through HPT and GH/IGF axes that cannot be recovered after depuration. ENR accumulates in the muscles of juvenile grass carp and may pose a threat to human health. Therefore, exposure of juvenile grass carp to ENR results in impaired thyroid function and impaired growth. In addition, consumption of ENR-exposed fish poses human health risks.

Toxic Effects on Thyroid Gland of Male Adult Lizards (Podarcis Siculus) in Contact with PolyChlorinated Biphenyls (PCBs)-Contaminated Soil.

Skin exposure is considered a potentially significant but little-studied pathway for PolyChlorinated Biphenyls uptake in terrestrial reptiles. In this study, a native Italian lizard, Podarcis siculus, was exposed to PCBs-contaminated soil for 120 days. Tissues distribution of PCBs, thyroid hormone levels, and thyroid histo-physiopathology were examined. The accumulation of PCBs in skin, plasma, liver, kidney, and brain were highest at 120 days. The alteration of triiodothyronine (T3) and thyroxine (T4) levels after different concentrations and times to exposure of PCBs was accompanied by the changes in the hormones involved in the hypothalamus-pituitary-thyroid (HPT) axis, namely Thyrotropin Releasing Hormone (TRH) and Thyroid Stimulating Hormone (TSH). Moreover, hepatic levels of deiodinase II (5′ORDII) and content of T3 were positively correlated to exposure to PCBs. These results indicated that in lizards, PCBs exposure through the skin has the potential to disrupt the thyroid endocrine system. Overall, the observed results indicate that PCBs could be associated with changes in thyroid homeostasis in these reptiles, through direct interactions with the metabolism of T4 and T3 through the HPT axis or indirect interactions with peripheral deiodination.

Comparative Study on Medicinal Natures (qi) of Black Ginseng, Red Ginseng, and Ginseng Leaves Based on Typical Deficiency-Heat Syndrome Rat Model.

To elucidate the medicinal nature of black ginseng (BG) by comparison of the effects of four Chinese herbs with different medicinal natures on the deficiency-heat syndrome rat model which was established by intragastric administration of traditional Chinese drugs with hot nature, the appearance indexes, biochemical indexes, and pathological sections of thyroid and stomach were examined. In addition, the seven short-chain fatty acids (SCFAs) in rat feces were also determined by headspace gas chromatography-mass spectrometry to reveal the action mechanism of the drugs with different natures. Results indicated that all the 4 drugs could exhibit similar actions in regulating the biochemical indexes of triiodothyronine (T3), thyroxine (T4), thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), and corticosterone (CORT) representing the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-adrenal (HPA) axes of the animal. However, cold-natured cortex phellodendri (HB) and ginseng leaves (GLs) showed stronger downregulation of the AChE activity of the nervous system. Red ginseng (RG) and BG tested exhibited stronger upregulation of the liver Na+-K+-ATPase activity. Principal component analysis (PCA) showed that GLs are similar to those of HB which belongs to the cold-nature drug, whereas BG showed closer to RG which attributes to a warm-nature drug. Thus, BG could be ascribed to a warm-nature drug. Further research disclosed that RG and BG mainly regulated the acetic acid and GL and HB primarily modulated the isovaleric acid and hexanoic acid in rat feces, which could be the features of drugs with warm or cold nature on the regulation of SCFAs in rats. It is for the first time that the medicinal nature of BG and its effect on the SCFAs were examined.

β-Ionone causes endocrine disruption, hyperpigmentation and hypoactivity in zebrafish early life stages

In nature, the odorous substance β-ionone has been widely detected in aquatic ecosystems. However, little is known about its ecotoxicological effects on freshwater vertebrates. In this study, we aimed to assess the acute toxicity of β-ionone in zebrafish (Danio rerio) embryos from 2 to 120 h post fertilization (hpf) and investigate embryo development, locomotor behavior and pigmentation under different concentrations. The results showed that exposure to β-ionone had an acute toxicity to early life stages of zebrafish and induced a decrease in hatching rate and an increase in the mortality and malformation rate. The median lethal concentration (LC50) of β-ionone at 96 h was observed as 1321 μg/L. In addition, β-ionone not only affected the body length of zebrafish larvae but also regulated the transcription of genes and the levels of hormones involved in the growth hormone/insulin-like growth factor (GH/IGF) and the hypothalamic-pituitary-thyroid (HPT) axes. Moreover, exposure to β-ionone induced significant decreases in locomotor activity and catecholamine neurotransmitters levels. Furthermore, β-ionone stimulated pigmentation via regulation of tyrosinase activity and melanin-related gene expression. Overall, this research could provide new insights into the potential risk of odorants to aquatic organisms.

PFOS-induced thyroid hormone system disrupted rats display organ-specific changes in their transcriptomes

Perfluorooctanesulfonic acid (PFOS) is a persistent anthropogenic chemical that can affect the thyroid hormone system in humans and animals. In adults, thyroid hormones (THs) are regulated by the hypothalamic-pituitary-thyroid (HPT) axis, but also by organs such as the liver and potentially the gut microbiota. PFOS and other xenobiotics can therefore disrupt the TH system at various locations and through different mechanisms. To start addressing this, we exposed adult male rats to 3 mg PFOS/kg/day for 7 days and analysed effects on multiple organs and pathways simultaneously by transcriptomics. This included four primary organs involved in TH regulation, namely hypothalamus, pituitary, thyroid, and liver. To investigate a potential role of the gut microbiota in thyroid hormone regulation, two additional groups of animals were dosed with the antibiotic vancomycin (8 mg/kg/day), either with or without PFOS. PFOS exposure decreased thyroxine (T4) and triiodothyronine (T3) without affecting thyroid stimulating hormone (TSH), resembling a state of hypothyroxinemia. PFOS exposure resulted in 50 differentially expressed genes (DEGs) in the hypothalamus, 68 DEGs in the pituitary, 71 DEGs in the thyroid, and 181 DEGs in the liver. A concomitant compromised gut microbiota did not significantly change effects of PFOS exposure. Organ-specific DEGs did not align with TH regulating genes; however, genes associated with vesicle transport and neuronal signaling were affected in the hypothalamus, and phase I and phase II metabolism in the liver. This suggests that a decrease in systemic TH levels may activate the expression of factors altering trafficking, metabolism and excretion of TH. At the transcriptional level, little evidence suggests that the pituitary or thyroid gland is involved in PFOS-induced TH system disruption.

Human adaptative behavior to Antarctic conditions: A review of physiological aspects.

The Antarctic environment induces adaptive metabolic and neuroendocrine changes associated with survival, as well as increased risks to physical and mental health. Circadian disruption has been observed in Antarctic expeditioners. The main consequences appear in quality of sleep, which can affect physical and cognitive performance. Physiological adaptation to cold is mediated by the norepinephrine and thyroid hormones (T3 and 3,5-T2 metabolite). The observed changes in the hypothalamic-pituitary-thyroid (HPT) axis of expeditioners varied according to temperature, photoperiod, time spent in the cold environment and stress level. The decrease in T3 levels has frequently been associated with mood swings. Psychological and physical stressors cause disturbances in the hypothalamic-pituitary-adrenal (HPA) axis, with consequent maintenance of high cortisol levels, leading to memory impairment, immunosuppression, and cardiometabolic and reproductive disorders. Preventive measures, such as provision of adequate food, well-established eating times, physical activity and even the use of phototherapy, can all help maintain the circadian rhythm. In addition, the use of high-tech clothing and room temperature control in research stations provide greater protection against the effects of intense cold. However, psychological stress requires a more individualized approach based on the crew's sociocultural characteristics, but it can be mitigated by mental healthcare and training in coping strategies. This article is categorized under: Cardiovascular Diseases > Molecular and Cellular Physiology Cardiovascular Diseases > Environmental Factors Metabolic Diseases > Environmental Factors.

Developmental toxicity of glyphosate on embryo-larval zebrafish (Danio rerio)

Glyphosate (GLY) induces developmental toxicity in fish, but research on the toxicity mechanism is limited. In this study, zebrafish embryos were exposed for 120 hpf to 0.7, 7, and 35 mg L-1 GLY. The results show that GLY treatment induced developmental toxicity in the fish, including premature hatching, reduced heartbeats, pericardial and yolk sac oedema, swim bladder deficiency, and shortened body length, which was possibly due to a significantly decreased triiodothyronine (T3)/thyroxine (T4) ratio and the abnormal expression patterns of hypothalamic-pituitary-thyroid (HPT) (crh, tshβ, tr α, tr β, and t tr ) and growth hormone/insulin-like growth factor (GH/IGF) axis-related genes (gh, ghrα, ghrβ, igf1, igf1rα, and igf1rβ) in larvae exposed to GLY. In addition, GLY exposure altered the levels of SOD and CAT, increased ROS, promoted malondialdehyde (MDA) content, and significantly altered the levels of endoplasmic reticulum (ER) stress signalling pathway factors (perk, eif2α, gadd34, atf4, ire1α, xbp1, atf6, hspa5, and chop), suggesting that GLY treatment induced oxidative injury and ER stress in the larvae. Further research showed that treatment with a higher concentration of GLY upregulated the levels of iNOS, IL-1β, and TNF-α while inhibiting the expression of IL-10 and TGF-β, suggesting that GLY causes an inflammatory reaction in the larvae. In addition, we also found that apoptosis was induced in the larvae, which was determined by acridine orange staining and abnormal expression of p53, caspase-3, -8, and -9. Taken together, our results demonstrate that GLY exposure altered the T3/T4 ratio, disturbed the expression patterns of HPT and GH/IGF axis-related genes, and induced oxidative and ER stress, inflammatory reactions, and apoptosis in the zebrafish larvae. This investigation contributes to improved understanding of the developmental toxicity mechanism of GLY in fish.

Post-COVID-19 Condition: Where Are We Now?

COVID-19 is currently considered a systemic infection involving multiple systems and causing chronic complications. Compared to other post-viral fatigue syndromes, these complications are wider and more intense. The most frequent symptoms are profound fatigue, dyspnea, sleep difficulties, anxiety or depression, reduced lung capacity, memory/cognitive impairment, and hyposmia/anosmia. Risk factors for this condition are severity of illness, more than five symptoms in the first week of the disease, female sex, older age, the presence of comorbidities, and a weak anti-SARS-CoV-2 antibody response. Different lines of research have attempted to explain these protracted symptoms; chronic persistent inflammation, autonomic nervous system disruption, hypometabolism, and autoimmunity may play a role. Due to thyroid high ACE expression, the key molecular complex SARS-CoV-2 uses to infect the host cells, thyroid may be a target for the coronavirus infection. Thyroid dysfunction after SARS-CoV-2 infection may be a combination of numerous mechanisms, and its role in long-COVID manifestations is not yet established. The proposed mechanisms are a direct effect of SARS-CoV-2 on target cells, an indirect effect of systemic inflammatory immune response, and a dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis leading to decreased serum TSH. Only a few studies have reported the thyroid gland status in the post-COVID-19 condition. The presence of post-COVID symptoms deserves recognition of COVID-19 as a cause of post-viral fatigue syndrome. It is important to recognize the affected individuals at an early stage so we can offer them the most adequate treatments, helping them thrive through the uncertainty of their condition.

Exposure to diclofenac alters thyroid hormone levels and transcription of genes involved in the hypothalamic–pituitary–thyroid axis in zebrafish embryos/larvae

Diclofenac (DCF), one of typical non-steroidal anti-inflammatory drugs (NSAIDs), has been frequently detected in various environmental media. Nevertheless，the potential endocrine disrupting effects of DCF on fish were poorly understood. In the present study, zebrafish embryos/larvae were used as a model to evaluate the adverse effects of DCF on development and thyroid system. The results demonstrated that DCF only significantly decreased the heart rate at 72 h post-fertilization (hpf), exhibiting limited influence on the embryonic development of zebrafish. Treatment with DCF significantly reduced whole-body thyroxine (T4) levels, and changed transcriptional levels of several genes related to the hypothalamic-pituitary-thyroid (HPT) axis. These findings provide important information regarding to the mechanisms of DCF-induced developmental toxicity and thyroid disruption in fish.

Thyroid hormones disturbances, cognitive deficits and abnormal dynamic functional connectivity variability of the amygdala in unmedicated bipolar disorder

ObjectiveAccumulating evidence suggests that hypothalamus-pituitary-thyroid (HPT) axis dysfunction is relevant to the neuropsychological and pathophysiology functions of bipolar disorder (BD). However, no research has investigated the inter-relationships among thyroid hormones disturbance, neurocognitive deficits, and aberrant brain function (particularly in the amygdala) in patients with BD. Materials and methodsData of dynamic resting-state functional connectivity (rs-dFC) were gathered from 59 patients with unmedicated BD II during depressive episodes and 52 healthy controls (HCs). Four seeds were selected (the bilateral lateral amygdala and the bilateral medial amygdala). The sliding-window analysis was applied to investigate dynamic functional connectivity (dFC). Additionally, the serum thyroid hormone (free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4) and thyroid-stimulating hormone (TSH)) levels, and cognitive scores on the MATRICS Consensus Cognitive Battery (MCCB) in patients and HCs were detected. ResultsThe BD group exhibited increased dFC variability between the left medial amygdala and right medial prefrontal cortex (mPFC) when compared with the HC group. Additionally, the BD group showed lower FT3, TT3, and TSH level, higher FT4 level, and poorer cognitive score. Moreover, a significant negative correlation was observed between the dFC variability of the left medial amygdala-right mPFC and TSH level, or reasoning and problem solving of MCCB score in BD group. Multiple regression analysis showed that the TSH level × dFC variability of the medial amygdala-mPFC was an independent predictor for cognitive processing speed in BD group. ConclusionsThis study revealed patients with BD II depression had excessive variability in dFC between the medial amygdala and mPFC. Moreover, both HPT axis dysfunction and abnormal dFC of the amygdala-mPFC might be implicated in cognitive impairment in the early stages of BD.

Iodine deficiency is associated with increased thyroid hormone sensitivity in individuals with elevated TSH.

ObjectiveCentral sensitivity of thyroid hormone refers to the sensitivity of hypothalamic–pituitary–thyroid (HPT) axis to the change in circulating free thyroxine (fT4). A complex relationship exists between thyroxine levels and iodine nutritional status. To explore the relationship between thyroid hormone sensitivity and iodine nutritional status in elevated thyrotropin (TSH), we used national data to assess the relationship between thyroid hormone sensitivity and iodine nutritional status with contrasting demographic characteristics in China.MethodsWe enrolled 12,197 participants with TSH > 4.2 mIU/L from China. Serum and urine samples were collected, and we measured serum fT4, TSH, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) levels and urinary iodine concentration (UIC). The thyroid hormone sensitivity indices were calculated based on fT4 and TSH. The thyroid feedback quantile-based index (TFQI) is a new index to reflect thyroid hormone sensitivity. Higher TFQI quartiles indicated lower thyroid hormone sensitivity.ResultsThe odds ratios (ORs) for the fourth versus first TFQI quartile were 0.84 (95% CI 0.72–0.99) for iodine deficiency, 1.24 (95% CI 1.05–1.47) for TPOAb+, and 0.44 (95% CI 0.40–0.50) for females. The OR of the fourth and first TFQI quartiles for age <30 years and >60 years was 2.09 (95% CI 1.82–2.41) and 1.19 (95% CI 1.05–1.36), respectively (P < 0.05). Other thyroid sensitivity indices also yielded similar results.ConclusionThyroid hormone sensitivity and age have a U-shaped association in individuals with elevated TSH. Increased thyroid hormone sensitivity is associated with iodine deficiency and the female gender. Decreased thyroid hormone sensitivity is associated with TPOAb+. These findings are interesting and potentially useful for understanding the interaction between iodine nutrition and the hypothalamic–pituitary–thyroid axis.