Altered Thyroid Hormone Levels Research Articles

Associations between urinary phthalate metabolites and bisphenol A levels, and serum thyroid hormones among the Korean adult population - Korean National Environmental Health Survey (KoNEHS) 2012-2014.

Phthalates and bisphenol A (BPA) have been used extensively in many consumer products, resulting in widespread exposure in the general population. Studies have suggested associations between exposure to phthalates and BPA, and serum thyroid hormone levels, but confirmation on larger human populations is warranted. Data obtained from nationally representative Korean adults (n=6003) recruited for the second round of the Korean National Environmental Health Survey (KoNEHS), 2012-2014, were employed. Three di-(2-ethylhexyl) phthalate (DEHP) metabolites, along with benzyl-butyl phthalate (BBzP) and di-butyl phthalate (DBP) metabolites, and BPA were measured in subjects' urine. Thyroxine (T4), total triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured in serum. The associations between urinary phthalates or BPA and thyroid hormone levels were determined. Urinary phthalate metabolites were generally associated with lowered total T4 or T3, or increased TSH levels in serum. Interquartile range (IQR) increases of mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were associated with a 3.7% increase of TSH, and a 1.7% decrease of total T4 levels, respectively. When grouped by sex, urinary MEHHP levels were inversely associated with T4 only among males. Among females, mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP) levels were inversely associated with TSH and T3, respectively. In addition, negative association between BPA and TSH was observed. Several phthalates and BPA exposures were associated with altered circulatory thyroid hormone levels among general Korean adult population. Considering the importance of thyroid hormones, public health implications of such alteration warrant further studies.

Thyroid Hormone Levels in Chronic Alcoholic Liver Disease Patients Before and After Treatment.

Alcoholic liver disease affects almost all aspects of the thyroid gland including the thyroid hormone levels and the thyroid gland size. The altered thyroid hormone levels in alcoholic liver disease may affect alcohol abstinence in withdrawal period by changing hormone milieu in brain, increasing withdrawal dysphoria and increasing craving. The aim of the present study was to assess and compare the levels of thyroid hormones- free T3, free T4, Thyroid Stimulating Hormone (TSH) and Gamma Glutamyl Transferase (GGT) in chronic alcoholic liver disease patients before and after treatment. This study was conducted on 70 alcoholic liver disease patients. Two serum samples were taken from the patient once at the time of admission and the other at the time of discharge after atleast ten days of treatment. Serum free T3, free T4, TSH and GGT were assessed on auto analyzer Beckman Coulter. Statistical analysis is done by paired t-test and Pearson's Correlation test. In present study, serum GGT levels decreased significantly (before treatment-207.46±66.90 U/L; after treatment-78.47±19.71 U/L) and free T3 levels increased significantly with treatment (before treatment-2.54±0.48 pg/mL; after treatment-2.88±0.37 pg/mL). Free T4 levels are also increased with treatment (before treatment-0.78±0.19 ng/dL; after treatment-0.88±0.13 ng/dL) and TSH levels are not altered significantly with treatment (before treatment-3.34±1.62 μIU/mL; after treatment-3.32±1.51 μIU/mL). Additionally, free T3 showed a significant correlation with GGT before (p-value<0.001) and after treatment (p-value-0.003) and free T4 and TSH showed a significant correlation with GGT after treatment (free T4: p-value<0.001) (TSH: p-value <0.001) and a suggestive significance exists before treatment (free T4: p-value= 0.098) (TSH: p-value=0.062). Thyroid hormones levels, particularly free T3 and free T4, need to be evaluated in chronic alcoholic liver disease patients. Free T3 could be used as a marker of alcoholism and is very useful in assessing the treatment efficacy in chronic alcoholic liver disease. Also, assessing free thyroid hormones is necessary during the withdrawal and abstinent periods as decreased hormone levels may increase withdrawal effects and craving for alcohol.

Former Very Preterm Infants Show Alterations in Thyroid Function at a Preschool Age.

Preterm birth is frequently associated with altered thyroid hormone levels in the newborn period. Recent data suggest a role of prematurity independent of birth size also in childhood thyroid dysfunction. Whether the high-risk population of former very preterm infants (VPI) is particularly susceptible to thyroid hormone alterations is currently unknown. The aim of the present study was to assess whether former VPI display changes in thyroid hormone status in comparison to term-born controls at a preschool age. Free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) concentrations were determined in former VPI and same-aged children born at term at five to seven years of age. 31 former term infants and 82 former VPI were included in the study. In comparison to children born at term, former VPI had lower fT4 (16.1 ± 1.8 versus 17.0 ± 2.1 pmol/l), higher fT3 (6.8 ± 0.7 versus 6.5 pmol/l), and higher TSH levels (3.0 ± 1.4 versus 2.3 ± 1.0 μU/l), independent of major neonatal morbidities. As subclinical changes in thyroid hormone status are potentially associated with adverse health profiles, close follow-up of these children is warranted.

Genomics and CSF analyses implicate thyroid hormone in hippocampal sclerosis of aging

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer's neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer's Coordinating Center/Alzheimer's Disease Genetic Consortium data; n=2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain atrophy visualized by MRI (Alzheimer's Disease Neuroimaging Initiative data; n=1239). In human brain samples from the Braineac database, both rs704180 and rs73069071 risk genotypes were associated with variation in expression of ABCC9, a gene which encodes a metabolic sensor protein in astrocytes. The rs73069071 risk genotype was also associated with altered expression of a nearby astrocyte-expressed gene, SLCO1C1. Analyses of human brain gene expression databases indicated that the chromosome 12p12 locus may regulate particular astrocyte-expressed genes induced by the active form of thyroid hormone, triiodothyronine (T3). This is informative biologically, because the SLCO1C1 protein transports thyroid hormone into astrocytes from blood. Guided by the genomic data, we tested the hypothesis that altered thyroid hormone levels could be detected in cerebrospinal fluid (CSF) obtained from persons with HS pathology. Total T3 levels in CSF were elevated in HS cases (p<0.04 in two separately analyzed groups), but not in Alzheimer's disease cases, relative to controls. No change was detected in the serum levels of thyroid hormone (T3 or T4) in a subsample of HS cases prior to death. We conclude that brain thyroid hormone perturbation is a potential pathogenetic factor in HS that may also provide the basis for a novel CSF-based clinical biomarker.

Associations between repeated measures of thyroid hormone parameters in pregnancy and preterm birth

INTRODUCTION: Recent research has shown the potential for certain endocrine-disrupting chemicals to alter thyroid hormone levels in pregnant women. The adverse effects of overt maternal thyroid dis...

Role of endoplasmic reticulum stress-induced apoptosis in rat thyroid toxicity caused by excess fluoride and/or iodide.

Excess fluoride and iodide coexist in drinking water in many regions, but few studies have investigated the single or interactive effects on thyroid in vivo. In our study, Wistar rats were exposed to excess fluoride and/or iodide through drinking water for 2 or 8 months. The structure and function of the thyroid, cells apoptosis and the expression of inositol-requiring enzyme 1 (IRE1) pathway-related factors were analyzed. Results demonstrated that excess fluoride and/or iodide could change thyroid follicular morphology and alter thyroid hormone levels in rats. After 8 months treatment, both single and co-exposure of the two microelements could raise the thyroid cells apoptosis. However, the expressions of IRE1-related factors were only increased in fluoride-alone and the combined groups. In conclusion, thyroid structure and thyroid function were both affected by excess fluoride and/or iodide. IRE1-induced apoptosis were involved in this cytotoxic process caused by fluoride or the combination of two microelements.

Phenols and parabens in relation to reproductive and thyroid hormones in pregnant women

IntroductionPhenols and parabens are ubiquitous environmental contaminants. Evidence from animal studies and limited human data suggest they may be endocrine disruptors. In the current study, we examined associations of phenols and parabens with reproductive and thyroid hormones in 106 pregnant women recruited for the prospective cohort, “Puerto Rico Testsite for Exploring Contamination Threats (PROTECT)”. MethodsUrinary exposure biomarkers (bisphenol A, triclosan, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, butyl, methyl and propyl paraben) and serum hormone levels (estradiol, progesterone, sex hormone-binding globulin (SHBG), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone) were measured at up to two time points during pregnancy (16–20 weeks and 24–28 weeks). We used linear mixed models to assess relationships between exposure biomarkers and hormone levels across pregnancy, controlling for urinary specific gravity, maternal age, BMI and education. In sensitivity analyses, we evaluated cross-sectional relationships between exposure and hormone levels stratified by study visit using linear regression. ResultsAn IQR increase in methyl paraben was associated with a 7.70% increase (95% CI 1.50, 13.90) in SHBG. Furthermore, an IQR increase in butyl paraben as associated with an 8.46% decrease (95% CI 16.92, 0.00) in estradiol, as well as a 9.34% decrease (95% CI −18.31,−0.38) in estradiol/progesterone. Conversely, an IQR increase in butyl paraben was associated with a 5.64% increase (95% CI 1.26, 10.02) in FT4. Progesterone was consistently negatively associated with phenols, but none reached statistical significance. After stratification, methyl and propyl paraben were suggestively negatively associated with estradiol at the first time point (16–20 weeks), and suggestively positively associated with estradiol at the second time point (24–28 weeks). ConclusionsWithin this ongoing birth cohort, certain phenols and parabens were associated with altered reproductive and thyroid hormone levels during pregnancy. These changes may contribute to adverse health effects in mothers or their offspring, but additional research is required.

Lateral habenula as a link between thyroid and serotoninergic system modiates depressive symptoms in hypothyroidism rats.

Depression-like behavior is observed in both rats and people with hypothyroidism, which suggests that altered thyroid hormone levels are closely associated with mental illness. Furthermore, decreased serotonin (5-hydroxytryptamine, 5-HT) levels are found in some brain regions of hypothyroid rats with depression-like behavior. However, the mechanism underlying the effects of hypothyroidism on the central serotonin system is unclear. The lateral habenula (LHb) is related to both the serotonin and thyroid systems and also plays an important role in the pathogenesis of depression. Our study aimed to disclose the role of the LHb in the onset of depression-like behavior in thyroidectomy (TD) rats. Forced swimming (FST) and open-field tests (OFT) were performed to measure behavioral changes in TD rats. The expression of β calmodulin-dependent protein kinase type II (β CaMKII) in the LHb, cytochrome C oxidase (COX) activity in the LHb and dorsal raphe nucleus (DRN), and 5-HT levels in the DRN were assayed. We found that TD rats exhibited depression-like behavior in the FST and OFT. Compared with the sham group, neural activity and the expression of β CaMKII in TD rats were higher in the LHb, and neural activity and 5-HT levels were lower in the DRN. Depressive behavior and decreased 5-HT levels in the DRN in TD rats were reversed by LHb lesioning. Our study indicates that depression-like behavior in TD rats can be attributed to decreased 5-HT levels in the DRN resulting from inhibition by an overactive LHb. The LHb mediates the effect of the thyroid system on 5-HT function in the DRN.

Exposure to2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) alters thyroid hormone levels and thyroid hormone-regulated gene transcription in manila clam Ruditapes philippinarum

Polybrominated diphenyl ethers (PBDEs) have the potential to disturb the thyroid endocrine system in vertebrates, but little is known about the disruptive effects of PBDEs on marine bivalves. In this study, we first examined the effects of BDE-47 exposure on growth of juvenile manila clams Ruditapes philippinarum. The result showed that 1.0 and 10 μg L−1 BDE-47 had adverse effects on 14-d shell-length growth of juvenile clams. Then, one-year-old adult clams were exposed to 0, 0.1 and 1 μg L−1 BDE-47 for 15 d. BDE-47 (1 μg L−1) exposure caused significant decreases of total T4 (thyroxine) by 40% and T3 (3,5,3′-triiodothyronine) by 75% concentrations in haemolymph of the clams. Transcription of genes involved in thyroid hormone synthesis and metabolism were also studied by quantitative RT-PCR. Gene expression levels of sodium iodide symporter (rp-NIS), iodothyronine deiodinase (rp-Deio) and thyroid peroxidase (rp-TPO) were increased in a dose-dependent manner at day 5 and day 10, while monocarboxylate transporter 8 (rp-Mct8) was downregulated at day 5, day 10 and day 15. The effect and preliminary mechanism observed in the present study were consistent with the results from previous studies on rodent and fish, implying that exposure to BDE-47 may pose threat to thyroid hormone homeostasis in bivalves through thyroid synthesis and metabolism pathways. This study may provide a first step towards understanding of the thyroid function disruptive effects of PBDEs on marine bivalves and the underlying mechanism across taxonomic groups and phyla.

Exposure to difenoconazole causes changes of thyroid hormone and gene expression levels in zebrafish larvae.

Difenoconazole was believed to induce a large suite of symptoms during zebrafish development, but little is known about the negative invisible effect known as endocrine disruption. In this study, zebrafish (Danio rerio) embryos were exposed to various concentrations of difenoconazole from fertilization to 120 h post-fertilization (hpf), and the whole body content of thyroid hormone and gene transcription in the hypothalamic-pituitary-thyroid (HPT) axis were investigated. Results showed thyroxine (T4) levels were significantly decreased, while triiodothyronine (T3) concentrations were not changed. Moreover, the mRNA transcription of corticotrophin-releasing hormone (crh), thyroid-stimulating hormone (tshβ), transthyretin (ttr), thyronine deiodinase (dio1 and dio2), uridine diphosphate glucuronosyltransferase (ugt1ab) in the HPT axis were significantly up-regulated, but the transcriptions of thyroglobulin (tg), sodium/iodide symporter (nis) and thyroid hormone receptors trβ were not changed. The overall results showed that exposure to difenoconazole could alter thyroid hormone levels and gene transcription in zebrafish larvae, indicating thyroid endocrine disruption.

Associations of birth outcomes with maternal polybrominated diphenyl ethers and thyroid hormones during pregnancy

BackgroundPrevious research has linked polybrominated diphenyl ether (PBDE) exposure to poor birth outcomes and altered thyroid hormone levels. ObjectivesWe examined whether maternal PBDE serum levels were associated with infant birth weight (g), head circumference (cm), birth length (cm), and birth weight percentile for gestational age. We explored the potential for a mediating role of thyroid hormone levels. MethodsDuring 2008–2010, we recruited 140 pregnant women in their third trimester as part of a larger clinical obstetrics study known as Healthy Pregnancy, Healthy Baby. Blood samples were collected during a routine prenatal clinic visit. Serum was analyzed for PBDEs, phenolic metabolites, and thyroid hormones. Birth outcome information was abstracted from medical records. ResultsIn unadjusted models, a two-fold increase in maternal BDE 153 was associated with an average decrease in head circumference of 0.32cm (95% CI: −0.53, −0.12); however, this association was attenuated after control for maternal risk factors. BDE 47 and 99 were similarly negatively associated but with 95% confidence intervals crossing the null. Associations were unchanged in the presence of thyroid hormones. ConclusionsOur data suggest a potential deleterious association between maternal PBDE levels and infant head circumference; however, confirmatory studies are needed in larger sample sizes. A mediating role of thyroid hormones was not apparent.

Pathophysiological aspects of thyroid hormone disorders/thyroid peroxidase autoantibodies and reproduction.

Thyroid hormone disorders and thyroid peroxidase autoantibodies (TPO-Ab) in women are associated with subfertility and early pregnancy loss. Here, we aim to provide a comprehensive overview of the literature on the pathophysiology of these associations. A review of the literature in the English language was carried out. Relevant studies were identified by searching Medline, EMBASE and the Cochrane Controlled Trials Register from 1975 until March 2014. From a total of 6108 primary selected articles from the literature search, 105 articles were selected for critical appraisal. Observational data indicate that altered thyroid hormone levels are associated with disturbed folliculogenesis, spermatogenesis, lower fertilization rates and lower embryo quality. Triiodothyronine (T3) in combination with FSH enhances granulosa cell proliferation and inhibits granulosa cell apoptosis by the PI3K/Akt pathway. T3 is considered a biological amplifier of the stimulatory action of gonadotrophins on granulosa cell function. T3 increases the expression of matrix metalloproteinases (MMP), MMP-2, MMP-3, fetal fibronectin and integrin α5β1T3 in early placental extravillous trophoblasts. Thyroid hormone transporters and receptors are expressed in the ovary, early embryo, endometrium, uterus and placenta. No other data explaining the associations could be retrieved from the literature. The presence of TPO-Ab is negatively associated with spermatogenesis, fertilization and embryo quality, but no data are available on the potential pathophysiological mechanisms. Thyroid hormone disorders and TPO-Ab are associated with disturbed folliculogenesis, spermatogenesis, fertilization and embryogenesis. The pathophysiology of these associations remains largely unknown, as evidence is limited and includes studies using small sample sizes, and often restricted to animal models. There are no studies on the pathophysiology underlying the association between TPO-Ab and reproduction. The available evidence, although limited, supports a role of thyroid hormone in fertility and early pregnancy. This justifies clinical intervention studies on the effects of thyroid hormone supplementation in women with subclinical hypothyroidism and in women prone to develop hypothyroidism due to the presence of TPO-Ab. In addition, more research is needed to identify the underlying mechanisms. This would be of particular interest in women undergoing IVF to pinpoint the effects of thyroid hormone on different parameters of reproduction.

Urinary phthalate metabolites in relation to maternal serum thyroid and sex hormone levels during pregnancy: a longitudinal analysis.

BackgroundIncreasing scientific evidence suggests that exposure to phthalates during pregnancy may be associated with an elevated risk of adverse reproductive outcomes such as preterm birth. Maternal endocrine disruption across pregnancy may be one pathway mediating some of these relationships. We investigated whether urinary phthalate metabolites were associated with maternal serum thyroid (free thyroxine [FT4], free triiodothyronine [FT3], and thyroid-stimulating hormone [TSH]), and sex (estradiol, progesterone, and sex hormone-binding globulin [SHBG]) hormone levels at multiple time points during pregnancy.MethodsPreliminary data (n = 106) were obtained from an ongoing prospective birth cohort in Northern Puerto Rico. We collected urine and serum sample at the first and third study visits that occurred at 18 +/- 2 and 26 +/- 2 weeks of gestation, respectively. To explore the longitudinal relationships between urinary phthalate metabolites and serum thyroid and sex hormone concentrations, we used linear mixed models (LMMs) adjusted for prepregnancy body mass index (BMI) and maternal age. An interaction term was added to each LMM to test whether the effect of urinary phthalate metabolites on serum thyroid and sex hormone levels varied by study visit. In cross-sectional analyses, we stratified BMI- and age-adjusted linear regression models by study visit.ResultsIn adjusted LMMs, we observed significant inverse associations between mono-3-carboxypropyl phthalate (MCPP) and FT3 and between mono-ethyl phthalate (MEP) and progesterone. In cross-sectional analyses by study visit, we detected stronger and statistically significant inverse associations at the third study visit between FT3 and MCPP as well as mono-carboxyisooctyl phthalate (MCOP); also at the third study visit, significant inverse associations were observed between FT4 and metabolites of di-(2-ethylhexyl) phthalate (DEHP). The inverse association between MEP and progesterone was consistent across study visits.ConclusionsIn this group of pregnant women, urinary phthalate metabolites may be associated with altered maternal serum thyroid and sex hormone levels, and the magnitude of these effects may depend on the timing of exposure during gestation.Electronic supplementary materialThe online version of this article (doi:10.1186/1477-7827-13-4) contains supplementary material, which is available to authorized users.

Relative developmental toxicities of pentachloroanisole and pentachlorophenol in a zebrafish model (Danio rerio)

Pentachloroanisole (PCA) and pentachlorophenol (PCP) are chlorinated aromatic compounds that have been found in the environment and in human populations. The objective of this study is to characterize the effects of PCA in comparison to those of PCP on development at environmental relevant levels using a fish model. Zebrafish embryos were exposed to 0.1, 1, 10, 100, 500, 1000μg/L PCA and PCP respectively for 96h. Malformation observation, LC50 testing for survival rate at 96 hours post fertilization (hpf) and EC50 testing for hatching rate at 72 hpf indicated that the developmental toxicity of PCP was about 15 times higher than that of PCA. PCP exposure at 10μg/L resulted in elevated 3, 3′, 5-triiodothyronine (T3) levels and decreased thyroxine (T4) levels, whereas PCA had no effects on T3 or T4 levels. PCP and PCA exposure at 1 and 10μg/L showed possible hyperthyroid effects similar to that of T3, due to increased relative mRNA expression of synapsin I (SYN), iodothyronine deiodinase type III (Dio3), thyroid hormone receptor alpha a (THRαa) and thyroid hormone receptor beta (THRβ), and decreased expression of iodothyronine deiodinase type II (Dio2). The results indicate that both PCA and PCP exposure can cause morphological deformities, possibly affect the timing and coordination of development in the central nervous system, and alter thyroid hormone levels by disrupting thyroid hormone regulating pathways. However, the developmental toxicity of PCA is at least ten times lower than that of PCP. Our results on the relative developmental toxicities of PCA and PCP and the possible underlying mechanisms will be useful to support interpretation of envrionmental concentrations and body burden levels observed in human populations.

Phthalate Exposure in Relation to Maternal Thyroid and Reproductive Hormone Levels during Pregnancy

There is increasing evidence that exposure to phthalates during pregnancy may elevate the risk of adverse reproductive outcomes such as preterm birth. Maternal endocrine disruption across pregnancy may be one pathway mediating some of these relationships. We investigated whether urinary phthalate metabolites were associated with maternal thyroid (thyroid-stimulating hormone [TSH], free thyroxine [FT4], and free triiodothyronine [FT3]) and reproductive (sex hormone-binding globulin [SHBG], progesterone, and estradiol) hormone levels at multiple time points during pregnancy. Preliminary data (n=106) were obtained from an ongoing prospective birth cohort in Northern Puerto Rico. We measured 11 urinary phthalate metabolite concentrations in urine samples collected up to three visits per subject during pregnancy (18±2, 22±2, and 26±2 weeks of gestation; N=293 total samples). We also measured thyroid and reproductive hormone concentrations in serum collected at up to two time points per subject during pregnancy (18±2 and 26±2 weeks of gestation). In adjusted linear mixed models, we observed significant inverse associations between mono-3-carboxypropyl phthalate (MCPP) and FT3 and between mono-ethyl phthalate (MEP) and progesterone. In cross-sectional analyses by study visit, we detected stronger and statistically significant inverse associations in the third visit between FT3 and MCPP as well as mono-carboxyisooctyl phthalate (MCOP), and between FT4 and metabolites of di-(2-ethylhexyl) phthalate (DEHP) compared to the corresponding results for the first visit. Negative effect estimates for MEP and progesterone were similar between study visits. Urinary phthalate metabolites may be associated with altered maternal thyroid and reproductive hormone levels during pregnancy. In particular, the potential thyroid-disrupting effects of phthalates may be more profound during the latter half of gestation.

Serum dioxin concentrations and thyroid hormone levels in the Seveso Women's Health Study.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant. Although experimental evidence suggests that TCDD alters thyroid hormone levels in rodents, human data are inconsistent. In 1976, a trichlorophenol plant exploded in Seveso, Italy. Women living in highly exposed areas were followed through the Seveso Women's Health Study. TCDD concentrations were measured in 1976 (n = 981) and 1996 (n = 260), and levels of total thyroxine, free thyroxine, free triiodothyronine, and thyroid-stimulating hormone were measured in 1996 (n = 909) and 2008 (n = 724). We used conditional multiple linear regression and marginal structural models with inverse-probability-of-treatment weights to evaluate associations and causal effects. TCDD concentration in 1976 was inversely associated with total thyroxine level in 1996 but not in 2008. Associations were stronger among women who had been exposed before menarche. Among these women, associations between total thyroxine and concurrent 1996 TCDD were slightly weaker than those with 1976 TCDD. A model including both 1976 and 1996 measurements strengthened the relationship between 1976 TCDD and total thyroxine but drove the association with 1996 TCDD to the null. TCDD exposure was not associated with levels of other thyroid hormones. TCDD exposure, particularly exposure before menarche, may have enduring impacts on women's total thyroxine levels. Initial exposure appears to be more influential than remaining body burden.

Gestational and lactational exposure to the polychlorinated biphenyl mixture Aroclor 1254 modulates retinoid homeostasis in rat offspring

Polychlorinated biphenyls (PCBs) induce a broad spectrum of biochemical and toxic effects in mammals including alterations of the vital retinoid (vitamin A) system. The aim of this study was to characterize alterations of tissue retinoid levels in rat offspring and their dams following gestational and lactational exposure to the PCB mixture Aroclor 1254 (A1254) and to assess the interrelationship of these changes with other established sensitive biochemical and toxicological endpoints. Sprague-Dawley rat dams were exposed orally to 0 or 15mg/kg body weight/day of A1254 from gestational day 1 to postnatal day (PND) 23. Livers, kidneys and serum were collected from the offspring on PNDs 35, 77 and 350. Tissue and serum retinoid levels, hepatic cytochrome P450 (CYP) enzymes and serum thyroid hormones were analyzed. A multivariate regression between A1254 treatment, hepatic retinoid levels, hepatic CYP enzymes activities, thyroid hormone levels and body/liver weights was performed using an orthogonal partial least-squares (PLS) analysis. The contribution of dioxin-like (DL) components of A1254 to the observed effects was also estimated using the toxic equivalency (TEQ) concept. In both male and female offspring short-term alterations in tissue retinoid levels occurred at PND35, i.e. decreased levels of hepatic retinol and retinoic acid (RA) metabolite 9-cis-4-oxo-13,14-dihydro-RA with concurrent increases in hepatic and renal all-trans-RA levels. Long-term changes consisted of decreased hepatic retinyl palmitate and increased renal retinol levels that were apparent until PND350. Retinoid system alterations were associated with altered CYP enzyme activities and serum thyroid hormone levels as well as body and liver weights in both offspring and dams. The estimated DL activity was within an order of magnitude of the theoretical TEQ for different endpoints, indicating significant involvement of DL congeners in the observed effects. This study shows that tissue retinoid levels are affected both short- and long-term by developmental A1254 exposure and are associated with alterations of other established endpoints of toxicological concern.

Alteration of Rat Fetal Cerebral Cortex Development after Prenatal Exposure to Polychlorinated Biphenyls

Polychlorinated biphenyls (PCBs) are environmental contaminants that persist in environment and human tissues. Perinatal exposure to these endocrine disruptors causes cognitive deficits and learning disabilities in children. These effects may involve their ability to interfere with thyroid hormone (TH) action. We tested the hypothesis that developmental exposure to PCBs can concomitantly alter TH levels and TH-regulated events during cerebral cortex development: progenitor proliferation, cell cycle exit and neuron migration. Pregnant rats exposed to the commercial PCB mixture Aroclor 1254 ended gestation with reduced total and free serum thyroxine levels. Exposure to Aroclor 1254 increased cell cycle exit of the neuronal progenitors and delayed radial neuronal migration in the fetal cortex. Progenitor cell proliferation, cell death and differentiation rate were not altered by prenatal exposure to PCBs. Given that PCBs remain ubiquitous, though diminishing, contaminants in human systems, it is important that we further understand their deleterious effects in the brain.

A Novel Deletion Mutation of SLC16A2 Encoding Monocarboxylate Transporter (MCT) 8 in a 26-year-old Japanese Patient with Allan-Herndon-Dudley Syndrome.

Allan-Herndon-Dudley Syndrome (AHDS), an X linked condition, is characterized by congenital hypotonia that progresses to spasticity with severe psychomotor delays, in combination with altered thyroid hormone levels, in particular, high serum T3 levels. Recently, this disease was proved to be caused by mutations in SLC16A2 coding for the monocarboxylate thyroid hormone transporter 8 (MCT8). Here we describe a 26-year -old Japanese patient with AHDS who had deletion of exon 3 of SLC16A2.

Thyroid endocrine disruption in zebrafish larvae following exposure to hexaconazole and tebuconazole

The widely used triazole fungicides have the potential to disrupt endocrine system, but little is known of such effects or underlying mechanisms of hexaconazole (HEX) and tebuconazole (TEB) in fish. In the present study, zebrafish (Danio rerio) embryos were exposed to various concentrations of HEX (0.625, 1.25 and 2.5mg/L) and TEB (1, 2 and 4mg/L) from fertilization to 120h post-fertilization (hpf). The whole body content of thyroid hormone and transcription of genes in the hypothalamic-pituitary-thyroid (HPT) axis were analyzed. The results showed that thyroxine (T4) levels were significantly decreased, while triiodothyronine (T3) concentrations were significantly increased after exposure to HEX and TEB, indicating thyroid endocrine disruption. Exposure to HEX significantly induced the transcription of all the measured genes (i.e., corticotrophin-releasing hormone (CRH), thyroid-stimulating hormone (TSHβ), sodium/iodide symporter (NIS), transthyretin (TTR), uridine diphosphate glucuronosyltransferase (UGT1ab), thyronine deiodinase (Dio1 and Dio2), thyroid hormone receptors (TRα and TRβ)) in the HPT axis, but did not affect the transcription of thyroglobulin (TG). However, TEB exposure resulted in the upregulation of all the measured genes, excepting that TG, Dio1and TRα had not changed significantly. The overall results indicated that exposure to HEX and TEB could alter thyroid hormone levels as well as gene transcription in the HPT axis in zebrafish larvae.