Sex-Dependent Claudin-1 Expression in the Liver of Euthyroid and Hypothyroid Mice

Zwanziger, Denise; Rakov, Helena; Engels, Kathrin; Moeller, Lars C.; Führer, Dagmar

doi:10.1159/000431316

Cited by 13 publications

(11 citation statements)

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“…In addition, studies on changes in other functional parameters in liver tissues revealed sex-dependent regulation of tight junction proteins, such as claudin-1 and claudin-2 in cholangiocytes and hepatocytes of male and female animals under hypothyroid conditions. Further experiments including analysis of CHO synthesis pathways led to the hypothesis that claudins may be relevant for reversal of sex hormone-related susceptibility to gallstone formation in hypothyroidism [ 6 ]. On the other hand, TG serum concentration increased in hyperthyroid female mice only (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic hyperthyroidism and hypothyroidism were induced as previously described [ 5 , 6 ]. Briefly, for hyperthyroidism, i.p.…”

Section: Methodsmentioning

confidence: 99%

“…As previously described [ 5 , 6 ], animals were euthanized 24 h after the last T 4 treatment or continuous TH deprivation. Liver, heart, and BAT were isolated and stored at −80 °C until further processing.…”

Section: Methodsmentioning

confidence: 99%

“…RNA extraction was performed as previously described [ 5 , 6 ]. Briefly, total RNA was extracted using RNeasy mini kit (Qiagen, Germany) and reversed transcribed using SuperScript III First-Strand Synthesis System for RT-PCR according to instruction manuals (Life Technologies, Germany).…”

Section: Methodsmentioning

confidence: 99%

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Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice

et al. 2016

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BackgroundThyroid dysfunction is more common in the female population, however, the impact of sex on disease characteristics has rarely been addressed. Using a murine model, we asked whether sex has an influence on phenotypes, thyroid hormone status, and thyroid hormone tissue response in hyper- and hypothyroidism.MethodsHypo- and hyperthyroidism were induced in 5-month-old female and male wildtype C57BL/6N mice, by LoI/MMI/ClO4− or T4 i.p. treatment over 7 weeks, and control animals underwent sham treatment (N = 8 animals/sex/treatment). Animals were investigated for impact of sex on body weight, food and water intake, body temperature, heart rate, behaviour (locomotor activity, motor coordination, and strength), liver function, serum thyroid hormone status, and cellular TH effects on gene expression in brown adipose tissue, heart, and liver.ResultsMale and female mice showed significant differences in behavioural, functional, metabolic, biochemical, and molecular traits of hyper- and hypothyroidism. Hyperthyroidism resulted in increased locomotor activity in female mice but decreased muscle strength and motor coordination preferably in male animals. Hypothyroidism led to increased water intake in male but not female mice and significantly higher serum cholesterol in male mice. Natural sex differences in body temperature, body weight gain, food and water intake were preserved under hyperthyroid conditions. In contrast, natural sex differences in heart rate disappeared with TH excess and deprivation. The variations of hyper- or hypothyroid traits of male and female mice were not explained by classical T3/T4 serum state. TH serum concentrations were significantly increased in female mice under hyperthyroidism, but no sex differences were found under eu- or hypothyroid conditions. Interestingly, analysis of expression of TH target genes and TH transporters revealed little sex dependency in heart, while sex differences in target genes were present in liver and brown adipose tissue in line with altered functional and metabolic traits of hyper- and hypothyroidism.ConclusionsThese data demonstrate that the phenotypes of hypo- and hyperthyroidism differ between male and female mice and indicate that sex is an important modifier of phenotypic manifestations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-016-0089-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Chronic hyperthyroidism and hypothyroidism were induced as previously described [ 5 , 6 ]. Briefly, for hyperthyroidism, i.p.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice

et al. 2016

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“…Canalicular water channels (AQPs) and tight junctions (TJs) facilitate osmotically driven water transport as well as paracellular barrier tightening and thereby influence biliary viscosity. In CGD, TJ proteins (e. g. Claudin 1-4, Occludin, Zonula occludens-1) and several AQPs, showed altered expression in human and murine gallbladder epithelium [40][41][42], whereas THs modulate hepatic Claudin and AQP expression [43,44].…”

Section: Thyroid Dysfunction Bile Flow and Viscositymentioning

confidence: 99%

Thyroid Dysfunction and Cholesterol Gallstone Disease

Kube

Zwanziger

2019

Exp Clin Endocrinol Diabetes

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Cholesterol gallstone disease (CGD) affects 10–15% of the adult population worldwide and the prevalence increases as a result of longer life expectancy as well as rising obesity in the general population. Beside well established CGD risk factors including environmental and genetic determinants (LITH genes), a correlation between thyroid dysfunction and CGD has been suggested in several human and murine studies. Although the precise underlying mechanisms are poorly understood, thyroid hormones may impact bile flow, bile composition and the maintenance of the enterohepatic circulation. Further there is evidence that thyroid hormones possibly impact LITH genes which are regulated by nuclear receptors (NRs). A better understanding of the CGD pathomechanisms might contribute to personalized prevention and therapy of highly prevalent and economically significant digestive disease. This review presents the current knowledge about the association between CGD and thyroid hormone dysfunction.

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Evidence of G-protein-coupled receptor and substrate transporter heteromerization at a single molecule level

Fischer

Kleinau

Rutz

et al. 2017

Cell. Mol. Life Sci.

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G-protein-coupled receptors (GPCRs) can constitute complexes with non-GPCR integral membrane proteins, while such interaction has not been demonstrated at a single molecule level so far. We here investigated the potential interaction between the thyrotropin receptor (TSHR) and the monocarboxylate transporter 8 (MCT8), a member of the major facilitator superfamily (MFS), using fluorescence cross-correlation spectroscopy (FCCS). Both the proteins are expressed endogenously on the basolateral plasma membrane of the thyrocytes and are involved in stimulation of thyroid hormone production and release. Indeed, we demonstrate strong interaction between both the proteins which causes a suppressed activation of G by TSH-stimulated TSHR. Thus, we provide not only evidence for a novel interaction between the TSHR and MCT8, but could also prove this interaction on a single molecule level. Moreover, this interaction forces biased signaling at the TSHR. These results are of general interest for both the GPCR and the MFS research fields.

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Sex-Dependent Claudin-1 Expression in the Liver of Euthyroid and Hypothyroid Mice

Abstract: compared to the euthyroid controls. Conclusion: We demonstrate a correlation between claudin-1 expression and hypothyroidism in the murine liver. Furthermore, a sex-dependent alteration of claudin-1 expression was found.

Cited by 13 publications

References 31 publications

Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice

Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice

Thyroid Dysfunction and Cholesterol Gallstone Disease

Evidence of G-protein-coupled receptor and substrate transporter heteromerization at a single molecule level

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