Thyroid Hormone Regulates Postnatal Development of the Rete Testis in Mice.

Thyroid hormone regulates the rate of testis maturation in mammals. Manipulations of thyroid hormone levels in neonatal animals affect various aspects of testis biology. However, there have been no studies examining the effects of thyroid hormone on the rete testis (RT). Here, we used animal models of neonatal hyperthyroidism (injections of triiodothyronine, or T3) and hypothyroidism (goitrogen 6-propyl-2-thiouracil [PTU] treatment) and found that higher levels of thyroid hormone accelerate RT development, while lower levels of thyroid hormone delay it. T3 and PTU treatments influence RT size, proliferation of RT cells, and expression of DMRT1 and androgen receptor in the RT. T3 supplementation accelerates RT development in an organ testicular culture, which indicates the local action of thyroid hormone. Additionally, it was found that follicle-stimulating hormone could be involved in the regulation both of RT proliferation and RT size. The fact that RT cells in a cell culture do not respond to T3 suggests indirect action of thyroid hormone on the RT in vivo or the loss of the responsiveness to the hormone in vitro.

The effects of PPARγ agonists on long­termpotentiation and apoptosis in the hippocampusarea of juvenile hypothyroid rats.

The aim of the present study was to evaluate the effect of rosiglitazone (RSG) or pioglitazone (POG) on the synaptic plasticity, neuronal apoptosis, brain-derived neurotrophic factor (BDNF), and nitric oxide (NO) metabolites in the hippocampus of juvenile hypothyroid rats. The animals were divided into four groups: control; propylthiouracil (PTU), 0.05% dose in drinking water for 42 days; PTU-POG; and PTU-RSG. The POG (20 mg/kg) and the RSG (4 mg/kg) were administered by IP injection. We conducted long­term potentiation (LTP) in the cornu ammonis 1 area of the hippocampus using high­frequency stimulation of the Schaffer collateral pathway. Then, the hippocampal tissues were collected to determine BDNF and NO levels and the degree of apoptosis. PTU administration decreased the slope (10-90%) and amplitude of the fEPSPs compared to control. Injection of RSG or POG increased the slope, slope (10-90%), and amplitude of the fEPSP in the PTU­POG or PTU­RSG groups compared to the PTU group. TUNEL­positive neurons and NO metabolites in the hippocampus of the PTU group were higher than those of the control group. RSG or POG increased BDNF content in PTU-POG or PTU-RSG groups. Treatment of the rats with POG or RSG decreased apoptotic neurons and NO metabolites in the hippocampus of PTU-POG or PTU-RSG groups, respectively, compared to the PTU group. This study's results revealed that POG or RSG normalized LTP impairment, neuronal apoptosis, and improved BDNF content in the hippocampal tissue of juvenile hypothyroid rats.

Mild exercise plus levothyroxine ameliorate deficits of spatial navigation, anxiety profile, and hippocampal BDNF in hypothyroid male offspring rats.

PURPOSE: Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams. METHOD: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 µg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated. FINDING: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone. CONCLUSION: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.

Investigating the mechanisms of action of thyroid disruptors: A multimodal approach that integrates in vitro and metabolomic analysis.

The thyroid gland, a vital component of the endocrine system, plays a pivotal role in regulating metabolic processes, growth, and development. To better characterize thyroid system disrupting chemicals (TSDC), we followed the next-generation risk assessment approach, which further considers the mechanistic profile of xenobiotics. We combined targeted in vitro testing with untargeted metabolomics. Four known TSDC, propyl-thiouracil (PTU), sodium perchlorate, triclosan, and 5-pregnen-3ß-ol-20-one-16α­carbonitrile (PCN) were investigated using rat in vitro models, including primary hepatocytes, PCCL3 cells, thyroid microsomes, and three-dimensional thyroid follicles. We confirmed each compound's mode of action, PTU inhibited thyroperoxidase activity and thyroid hormones secretion in thyroid cells model, sodium perchlorate induced a NIS-mediated iodide uptake decrease as triclosan to a lesser extent, and PCN activated expression and activity of hepatic enzymes (CYPs and UGTs) involved in thyroid hormones metabolism. In parallel, we characterized intracellular metabolites of interest. We identified disrupted basal metabolic pathways, but also metabolites directly linked to the compound's mode of action as tyrosine derivates for sodium perchlorate and triclosan, bile acids involved in beta-oxidation, and precursors of cytochrome P450 synthesis for PCN. This pilot study has provided metabolomic fingerprinting of dedicated TSDC exposures, which could be used to screen and differentiate specific modes of action.

A meta-analysis on polymorphic trait of taste perception mediated by TAS2R38 genotype.

The objective of this study is to review the association of TAS2R38 polymorphisms and taste phenotypes to bitter compounds (phenylthiocarbamide [PTC]/propylthiouracil [PROP]), and its association among persons who drink alcohol and individuals with smoking behavior. A literature search was carried out in PubMed, ScienceDirect, Cochrane, and Wiley online library databases using the keyword "(Bitter taste receptor genes OR TAS2R38) AND (PROP OR propylthiouracil) AND (PTC OR phenylthiocarbamide)," "(Bitter taste receptor genes OR TAS2R38) AND (alcohol)," "(Bitter taste receptor genes OR TAS2R38) AND (tobacco OR smoker)" to find articles evaluating the association of taste phenotypes and TAS2R38 polymorphisms, and its association among persons who drink alcohol and individuals with smoking behavior. The analysis show that TAS2R38 taster genotype (proline-alanine-valine [PAV] allele) was significantly (OR, 5.88; CI [3.87, 8.95], p < .001) associated with taster phenotype for bitter compounds (PTC/PROP), and TAS2R38 nontaster genotype (alanine-valine-isoleucine allele) was significantly (OR, 6.73; CI [4.57, 9.90], p < .001) associated with nontaster phenotype for bitter compounds. Further, TAS2R38 taster genotypes (PAV homozygotes and heterozygotes) were significantly associated with higher alcohol intake (OR, 5.15; 95% CI [2.66, 9.98]; p < .001) and among individuals with smoking behavior (OR, 1.73; 95% CI [1.24, 2.42]; p = .001). This suggests that TAS2R38 single nucleotide polymorphisms can be identified by clinically assessing taste phenotype status for bitter compounds and can be used as a potential therapeutic target in the prevention and treatment of harmful higher alcohol intake and smoking behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effect of in utero and lactational exposure to a thyroid hormone system disrupting chemical on mouse metabolome and brain transcriptome.

Mice were exposed to a low dose of the model thyroid hormone disruptor, propylthiouracil. Although this had only a modest effect on maternal thyroid hormones production, postnatal analysis of the pups' plasma by mass spectrometry and the brain striatum by RNA sequencing gave evidence of low lasting changes that could reflect an adverse effect on neurodevelopment. Overall, these methods proved to be sensitive enough to detect minor disruptions of thyroid hormone signalling in vivo.

High-intensity interval training ameliorates spatial and recognition memory impairments, reduces hippocampal TNF-alpha levels, and amyloid-beta peptide load in male hypothyroid rats.

Thyroid hormones are critical for healthy brain functions at every stage of life. Hypothyroidism can cause severe cognitive dysfunction in patients who do not receive adequate treatment. Although thyroid hormone replacement alleviates cognitive decline in hypothyroid patients, there are studies showing that there is no complete recovery. The aim of this study was to investigate the effects of high-intensity interval training (HIIT) in hypothyroid rats on spatial and recognition memory, neuroinflammation, amyloid-beta load and compare these effects with T3 replacement. Hypothyroidism was induced and maintained by administration of 6-n-propyl-2-thiouracil (PTU) with their drinking water to 6-weeks-old male Sprague-Dawley rats for 7 weeks. The animals exercised in the treadmill according to the HIIT protocol for four weeks. T3 was injected intraperitoneally daily during the last two weeks of the study. All animals performed in the elevated plus maze test, Morris water maze test, novel object recognition test, and rotarod motor performance test in the last week of the study and then the animals were sacrificed. Amyloid beta (1-42) and TNFα levels were measured in the prefrontal cortex and hippocampus by ELISA. Anxiety-like behaviors did not significantly differ between groups. T3 replacement with or without HIIT increased motor performance in PTU-treated rats. HIIT and/or T3 replacement increased the exercise performance. HIIT and/or T3 replacement alleviated spatial and recognition memory impairments and normalized TNFα and amyloid-beta levels in the hippocampus in hypothyroid rats. In summary, regular physical exercise may have potential benefits in preserving cognitive functions in hypothyroid patients.

Oxidation of anti-thyroid drugs and their selenium analogs by ABTS radical cation.

Lactoperoxidase was previously used as a model enzyme to test the inhibitory activity of selenium analogs of anti-thyroid drugs with 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a substrate. Peroxidases oxidize ABTS to a metastable radical ABTS•+, which is readily reduced by many antioxidants, including thiol-containing compounds, and it has been used for decades to measure antioxidant activity in biological samples. We showed that anti-thyroid drugs 6-n-propyl-2-thiouracil, methimazole, and selenium analogs of methimazole also reduced it rapidly. This reaction may explain the anti-thyroid action of many other compounds, particularly natural antioxidants, which may reduce the oxidized form of iodine and/or tyrosyl radicals generated by thyroid peroxidase thus decreasing the production of thyroid hormones. However, influence of selenium analogs of methimazole on the rate of hydrogen peroxide consumption during oxidation of ABTS by lactoperoxidase was moderate. Direct hydrogen peroxide reduction, proposed before as their mechanism of action, cannot therefore account for the observed inhibitory effects. 1-Methylimidazole-2-selone and its diselenide were oxidized by ABTS•+ to relatively stable seleninic acid, which decomposed slowly to selenite and 1-methylimidazole. In contrast, oxidation of 1,3-dimethylimidazole-2-selone gave selenite and 1,3-dimethylimidazolium cation. Accumulation of the corresponding seleninic acid was not observed.

Thyroidectomy and PTU-Induced Hypothyroidism: Effect of L-Thyroxine on Suppression of Spatial and Non-Spatial Memory Related Signaling Molecules.

BACKGROUND: The calcium/calmodulin protein kinase II (CaMKII) signaling cascade is crucial for hippocampus-dependent learning and memory. Hypothyroidism impairs hippocampus- dependent learning and memory in adult rats, which can be prevented by simple replacement therapy with L-thyroxine (thyroxine, T4) treatment. In this study, we compared animal models of hypothyroidism induced by thyroidectomy and treatment with propylthiouracil (PTU) in terms of synaptic plasticity and the effect on underlying molecular mechanisms of spatial and non-spatial types of memory. METHODS: Hypothyroidism was induced using thyroidectomy or treatment with propylthiouracil (PTU). L-thyroxin was used as replacement therapy. Synaptic plasticity was evaluated using in vivo electrophysiological recording. Training in the radial arm water maze (RAWM), where rats had to locate a hidden platform, generated spatial and non-spatial learning and memory. Western blotting measured signaling molecules in the hippocampal area CA1 area. RESULTS: Our findings show that thyroidectomy and PTU models are equally effective, as indicated by the identical plasma levels of thyroid stimulating hormone (TSH) and T4. The two models produced an identical degree of inhibition of synaptic plasticity as indicated by depression of long-term potentiation (LTP). For non-spatial memory, rats were trained to swim to a visible platform in an open swim field. Analysis of hippocampal area CA1 revealed that training, on both mazes, of control and thyroxine-treated hypothyroid rats, produced significant increases in the P-calcium calmodulin kinase II (P-CaMKII), protein kinase-C (PKCγ), calcineurin and calmodulin protein levels, but the training failed to induce such increases in untreated thyroidectomized rats. CONCLUSION: Thyroxine therapy prevented the deleterious effects of hypothyroidism at the molecular level.

Compromised conformation and kinetics of catalase in the presence of propylthiouracil: A biophysical study and alleviation by curcumin.

In the present study, the inhibitory effect of propylthiouracil (PTU) on bovine liver catalase (BLC) activity was studied in the presence of curcumin (CUR). The results suggest that the PTU-induced decrease in BLC activity was caused by a change in conformation of BLC with reduced α-helical content and decrease in zeta potential. Nevertheless, temperature-dependent activation of CUR protects the activity of BLC by restoring the secondary conformation and zeta potential of BLC. CUR inhibited the time-induced reduction in BLC activity and the protection was increased with increasing concentrations of CUR and found to be significant even from 1:0.1 molar ratios. The enzyme kinetics confirmed the high catalytic efficiency of BLC in presence of CUR than PTU. The protective role of CUR was due to the formation of a more stabilized complex as demonstrated by molecular docking, and fourier-transform infrared study. Isothermal titration calorimetric study supports for a favourable reaction between BLC and PTU or CUR due to the negative ΔH, and positive TΔS. Although the number of binding sites for PTU and CUR was found to be 10 and 7, respectively, the binding affinity between CUR and BLC is approximately 3.72 fold stronger than BLC-PTU complex. The increased melting temperature of BLC was noticed in presence of CUR suggesting the protective potential of CUR towards biomolecules. Indeed, this is the first biophysical study to describe the molecular mechanism of PTU-induced reduction in BLC activity and alleviation by CUR with detail kinetics. Thus, CUR can be further extended to other antioxidant enzymes or compromised biomolecules for therapeutic interventions.

Effect of 6-n-propyl-2-thiouracil or dexamethasone administration on the responses of antimicrobial components in goat milk to intramammary lipopolysaccharide infusion.

Heat stress impacts the immune system of dairy animals by altering the hypothalamic-pituitary-adrenal axis and thyroid function, leading to conditions such as hypothyroidism and hypercortisolism. This study aimed to elucidate the effect of hypothyroidism and hypercortisolism on the response of mammary innate immune function to inflammation caused by Escherichia coli in dairy goats. To induce hypothyroidism and hypercortisolism, we administered 6-n-propyl-2-thiouracil (PTU; for 21 days) and dexamethasone (DEX; for 5 days), respectively, to six goats each; six goats without treatment were used as the control group. After treatment, lipopolysaccharide (LPS) from E. coli O111 was infused into the mammary gland. Somatic cell counts (SCC) and levels of lactoferrin (LF), S100A7, immunoglobulin A (IgA), and interleukin-8 (IL-8) in milk until 7 days after LPS infusion were measured. An increase in SCC after LPS infusion was inhibited in both PTU and DEX groups, and an increase in LF after LPS infusion was inhibited in PTU group, compared with that in the control group. The results of the present study suggest that the recruitment of neutrophils and LF production decreased under hypothyroidism or hypercortisolism, which may be one of the causes underlying increased incidence of mastitis in dairy animals under heat stress conditions.

A Fine Regulation of the Hippocampal Thyroid Signalling Protects Hypothyroid Mice against Glial Cell Activation.

Adult-onset hypothyroidism is associated with learning and cognitive dysfunctions, which may be related to alterations in synaptic plasticity. Local reduced levels of thyroid hormones (THs) may impair glia morphology and activity, and promote the increase of pro-inflammatory cytokine levels mainly in the hippocampus. Given that neuroinflammation induces memory impairments, hypothyroidism-related glia dysfunction may participate in brain disorders. Thus, we investigated the mechanisms linking hypothyroidism and neuroinflammation, from a protective perspective. We induced hypothyroidism in adult C57BL/6J and wild-derived WSB/EiJ male mice by a seven-week propylthiouracil (PTU) treatment. We previously showed that WSB/EiJ mice were resistant to high-fat diet (HFD)-induced obesity, showing no neuroinflammatory response through adaptive abilities, unlike C57BL/6J. As PTU and HFD treatments are known to induce comparable inflammatory responses, we hypothesized that WSB/EiJ mice might also be protected against hypothyroidism-induced neuroinflammation. We showed that hypothyroid WSB/EiJ mice depicted no hippocampal neuroinflammatory response and were able to maintain their hippocampal thyroid signalling despite low circulatisng TH levels. In contrast, C57BL/6J mice exhibited disturbed hippocampal TH signalling, accompanied by neuroinflammation and memory impairment. Our results reinforce the preponderance of the hippocampal TH regulatory system over TH circulating levels in the hippocampal glial reactivity.

The effects of curcumin in learning and memory impairment associated with hypothyroidism in juvenile rats: the role of nitric oxide, oxidative stress, and brain-derived neurotrophic factor.

The effect of curcumin (Cur) on cognitive impairment and the possible role of brain tissue oxidative stress, nitric oxide (NO) levels, and brain-derived neurotrophic factor (BDNF) were investigated in juvenile hypothyroid rats. The juvenile rats (21 days old) were allocated into the following groups: (1) control; (2) hypothyroid (0.05% propylthiouracil (PTU) in drinking water); (3-5) hypothyroid-Cur 50, 100, and 150, which in these groups 50, 100, or 150 mg/kg, Cur was orally administered by gavage during 6 weeks. In the hypothyroid rats, the time elapsed and the traveled distance to locate the hidden platform in the learning trials of Morris water maze (MWM) increased, and on the probe day, the amount of time spent in the target quadrant and the distance traveled in there was decreased. Hypothyroidism also decreased the latency and increased the time spent in the darkroom of the passive avoidance (PA) test. Compared with the hypothyroid group, Cur enhanced the performance of the rats in both MWM and PA tests. In addition, Cur reduced malondialdehyde concentration and NO metabolites; however, it increased thiol content as well as the activity of catalase (CAT) and superoxide dismutase enzymes in both the cortex and hippocampus. Cur also increased hippocampal synthesis of BDNF in hypothyroid rats. The beneficial effects of Cur cognitive function in juvenile hypothyroid rats might be attributed to its protective effect against oxidative stress and potentiation of BDNF production.

Cooked common bean flour, but not its protein hydrolysate, has the potential to improve gut microbiota composition and function in BALB/c mice fed a high-fat diet added with 6-propyl-2-thiouracil.

Common bean has the potential to improve gut microbiota function due to its chemical composition and content of dietary fiber. This study evaluated the effect of cooked common bean (CCB) flour and its protein hydrolysate as part of a high-fat diet (HFD) added with 6-propyl-2-thiouracil (10 mg/kg/d), an inhibitor of thyroid hormone synthesis, on gut health of BALB/c mice. Forty-eight adult mice were divided into four groups: normal control; HFD; HFD plus CCB flour (346.6 g/kg of diet) (HFBF group) and HFD plus CCB protein hydrolysate (700 mg/Kg/d) (HFPH group). HFBF, but not HFPH, increased cecum weight, and the moisture, and lipids in the excreted feces, compared to control groups. Sequencing of the 16S rRNA gene of the cecal microbiota indicated changes in the beta-diversity between the HFBF and HFPH groups, compared to the normal control. The abundance of Bacteroidetes increased and the Firmicutes/Bacteroidetes ratio decreased in the HFBF compared to control groups. However, HFPH was not able to prevent the damage caused by a HFD to the gut bacterial communities. The OTUs enriched by HFBF were mainly assigned to members of the Muribaculaceae family, which shows potential to improve gut health. The intake of CCB flour improved intestinal health and modulated the composition and function of the cecal microbiota, attenuating the effects of the HFD, added wit 6-propyl-2-thiouracil, when fed to BALB/c mice.

Daily Exposure to a Cranberry Polyphenol Oral Rinse Alters the Oral Microbiome but Not Taste Perception in PROP Taster Status Classified Individuals.

Diet and salivary proteins influence the composition of the oral microbiome, and recent data suggest that TAS2R38 bitter taste genetics may also play a role. We investigated the effects of daily exposure to a cranberry polyphenol oral rinse on taste perception, salivary proteins, and oral microbiota. 6-n-Propylthiouracil (PROP) super-tasters (ST, n = 10) and non-tasters (NT, n = 10) rinsed with 30 mL of 0.75 g/L cranberry polyphenol extract (CPE) in spring water, twice daily for 11 days while consuming their habitual diets. The 16S rRNA gene sequencing showed that the NT oral microbiome composition was different than that of STs at baseline (p = 0.012) but not after the intervention (p = 0.525). Principal coordinates analysis using unweighted UniFrac distance showed that CPE modified microbiome composition in NTs (p = 0.023) but not in STs (p = 0.096). The intervention also altered specific salivary protein levels (α-amylase, MUC-5B, and selected S-type Cystatins) with no changes in sensory perception. Correlation networks between oral microbiota, salivary proteins, and sensory ratings showed that the ST microbiome had a more complex relationship with salivary proteins, particularly proline-rich proteins, than that in NTs. These findings show that CPE modulated the oral microbiome of NTs to be similar to that of STs, which could have implications for oral health.

Histopathological changes of parotid and larynx in hypothyroid rats: experimental study.

OBJECTIVES: In this study, we aimed to investigate the laryngeal and parotid histopathological alterations in rats with experimentally induced postnatal hypothyroidism. MATERIALS AND METHODS: 200-300 g weighed Wistar albino rats were included in this study. The rats were randomly divided into four groups: group 1 is control and the other groups are experimental groups. Food and water were supplied ad libitum in group 1, no medication was administered. Propylthiouracil (PTU) was administered intraperitoneally for 15 days in group 2; for 30 days in group 3, for 45 days in group 4. The larynx and parotid glands of the rats were removed and intracardiac blood samples were collected for thyroid-stimulating hormone (TSH) analysis under anesthesia (ketamine hydrochloride, 100 mg/kg) 24 h after the last PTU injection. The same procedures were done for the control group at day 46. Histopathological evaluation was done for all the specimens. RESULTS: While submucosal vascular dilatation was significantly higher in the experiment groups (p < 0.05), there was not a significant difference in lamina propria edema, inflammation, goblet cell loss, cilia loss between the groups in larynx specimens. In parotid gland specimens, serous asinus atrophy, stromal connective tissue increase were significantly higher in experiment groups (p < 0.05). In addition, there was a significant difference in nuclear morphology between control and experimental groups (p < 0.05). CONCLUSION: The results of the study showed that hypothyroidism may have effect on inflammatory procedure by causing vascular dilation in larynx and serous asinus atrophy nucleus changes, connective tissue increase in stroma in parotid gland.

Larval metamorphosis is inhibited by methimazole and propylthiouracil that reveals possible hormonal action in the mussel Mytilus coruscus.

Larval metamorphosis in bivalves is a key event for the larva-to-juvenile transformation. Previously we have identified a thyroid hormone receptor (TR) gene that is crucial for larvae to acquire "competence" for the metamorphic transition in the mussel Mytilus courscus (Mc). The mechanisms of thyroid signaling in bivalves are still largely unknown. In the present study, we molecularly characterized the full-length of two iodothyronine deiodinase genes (McDx and McDy). Phylogenetic analysis revealed that deiodinases of molluscs (McDy, CgDx and CgDy) and vertebrates (D2 and D3) shared a node representing an immediate common ancestor, which resembled vertebrates D1 and might suggest that McDy acquired specialized function from vertebrates D1. Anti-thyroid compounds, methimazole (MMI) and propylthiouracil (PTU), were used to investigate their effects on larval metamorphosis and juvenile development in M. coruscus. Both MMI and PTU significantly reduced larval metamorphosis in response to the metamorphosis inducer epinephrine. MMI led to shell growth retardation in a concentration-dependent manner in juveniles of M. coruscus after 4 weeks of exposure, whereas PTU had no effect on juvenile growth. It is hypothesized that exposure to MMI and PTU reduced the ability of pediveliger larvae for the metamorphic transition to respond to the inducer. The effect of MMI and PTU on larval metamorphosis and development is most likely through a hormonal signal in the mussel M. coruscus, with the implications for exploring the origins and evolution of metamorphosis.

The efficiency and safety of methimazole and propylthiouracil in hyperthyroidism: A meta-analysis of randomized controlled trials.

PURPOSE: The aim of this study was to evaluate the efficiency and safety of methimazole (MMI) and propylthiouracil (PTU) in the treatment of hyperthyroidism. METHODS: Articles were searched through the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and QVIP. The primary outcomes were clinical efficacy and thyroid hormone levels in MMI and PTU groups. The secondary outcomes were liver function indexes and adverse reactions in MMI and PTU groups. Results were expressed as weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs). The Begg test was applied to assess the publication bias. RESULTS: Totally, 16 randomized controlled trials were retained in this meta-analysis with 973 patients receiving MMI and 933 receiving PTU. The levels of triiodothyronine (T3) (WMD = -1.321, 95% CI: -2.271 to -0.372, P = .006), thyroxine (T4) (WMD = -37.311, 95% CI: -61.012 to -13.610, P = .002), Free T3 (FT3) (WMD = -1.388, 95% CI: -2.543 to -0.233, P = .019), Free T4 (FT4) (WMD = -3.613, 95% CI: -5.972 to -1.255, P = .003), and the risk of liver function damage (OR = 0.208, 95% CI: 0.146-0.296, P < .001) in the MMI group were lower than those in the PTU group. The thyroid-stimulating hormone level (WMD = 0.787, 95% CI: 0.380-1.194, P < .001) and the risk of hypothyroidism (OR = 2.738, 95% CI: 1.444-5.193, P = .002) were higher in the MMI group than those in the PTU group. CONCLUSIONS: Although MMI might have higher risk of hypothyroidism than PTU, the efficacy of MMI may be better than PTU in patients with hyperthyroidism regarding reducing T3, T4, FT3, and FT4 levels, decreasing the risk of liver function damage and increasing the level of thyroid-stimulating hormone. REGISTER NUMBER: osf.io/ds637 (https://osf.io/search/).

Developmental thyroid disruption causes long-term impacts on immune cell function and transcriptional responses to pathogen in a small fish model.

Current evidence suggests thyroid hormones (THs) impact development of the immune system, but few studies have explored the connection between the thyroid and immune systems, especially in fish. This is important as some environmental contaminants disrupt TH homeostasis and may thus have negative impacts on the immune system. To determine the long-term consequences of early life stage (ELS) hypothyroidism on immune function, fathead minnows were exposed to the model thyroid hormone suppressant propylthiouracil (PTU) from < 1 to 30 days post hatch. Fish were transferred to clean water and raised to adulthood (5-7 months post hatch) at which time, several aspects of immune function were evaluated. Ex vivo assessment of immune cell function revealed significant decreases (1.2-fold) in the phagocytic cell activity of PTU-treated fish relative to the controls. Fish were also injected with Yersinia ruckeri to evaluate their in vivo immune responses across a suite of endpoints (i.e., transcriptomic analysis, leukocyte counts, spleen index, hematocrit, bacterial load and pathogen resistance). The transcriptomic response to infection was significantly different between control and PTU-treated fish, though no differences in bacterial load or pathogen resistance were noted. Overall, these results suggest that early life stage TH suppression causes long-term impacts on immune function at the molecular and cellular levels suggesting a key role for TH signaling in normal immune system development. This study lays the foundation for further exploration into thyroid-immune crosstalk in fish. This is noteworthy as disruption of the thyroid system during development, which can occur in response to chemicals present in the environment, may have lasting effects on immune function in adulthood.

Syringic acid, a novel thyroid hormone receptor-ß agonist, ameliorates propylthiouracil-induced thyroid toxicity in rats.

The aim of this study was to evaluate the potential of syringic acid (SA) against propylthiouracil (PTU)-induced hypothyroidism in rats. SA at a prestandardized dose, 50 mg/kg/day, was orally administered to PTU-induced hypothyroid rats for 30 days, and alterations in the levels of serum triiodothyronine (T3 ), thyroxine (T4 ), thyrotropin (TSH), alanine transaminase (ALT), and aspartate transaminase (AST); tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); total cholesterol (CHOL) and triglycerides (TG); hepatic lipid peroxidation (LPO) and antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione content), as well as histological changes in liver and thyroid were examined. The molecular interactions of the ligand, SA, with thyroid-related protein targets, such as human thyroid hormone receptor ß (hTRß), and thyroid peroxidase (TPO) protein, were studied using molecular docking. Whereas in hypothyroid animals, T4 , T3 , and antioxidants were decreased, there was an increase in TSH, TNF-α, IL-6, ALT, AST, and hepatic LPO; administration of SA in PTU-induced animals reversed all these indices to near normal levels. SA also improved the histological features of liver and thyroid gland. Our study clearly demonstrates SA as a novel thyroid agonist for augmenting the thyroid functions in rats. Molecular docking analysis reveals that SA possesses good binding affinity toward both the targets, hTRß and TPO. Through this approach, for the first time we provide the evidence for SA as a novel thyroid agonist and suggest a receptor-mediated mechanism for its thyroid stimulatory potential.