Functional analysis of the angio-follicular unit of the mouse thyroid gland

Weber, Jonas; Rehders, Maren; Säftig, Paul; Verrey, François; Schweizer, Ulrich; Wirth, EK; Heuer, Heike; Brix, Klaudia

doi:10.1055/s-0035-1547747

Cited by 2 publications

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“…Thus, for LAT2 we found moderate staining mainly in the cytoplasm. Normally, plasma membrane localization would be expected for TH transporters exporting TH from thyrocytes (19,20). However, in our series LAT2 was mainly located in cytoplasmic structures, presumably in vesicles of the endocytic pathway, which might be linked to the hypothesis of an endo-lysosomal functioning protein of LAT2 in the thyroid.…”

Section: Discussionmentioning

confidence: 53%

Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism

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Synoracki

et al. 2017

European Journal of Endocrinology

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Downregulation of MCT8 in thyroid cancers qualifies MCT8 as a marker of thyroid differentiation. The more variable expression of LATs in distinct thyroid malignancies may be linked with other transporter properties relevant to altered metabolism in cancer cells, i.e. amino acid transport. Consistent upregulation of MCT8 in GD is in line with increased TH release in hyperthyroidism, an assumption supported by our results showing TSH-dependent upregulation of MCT8.

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Section: Discussionmentioning

confidence: 53%

Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism

Badziong

Ting

Synoracki

et al. 2017

European Journal of Endocrinology

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“…To determine possible roles of Taar1 during development, which might be related to differentiation of thyroid follicle cells and thyroid tissue morphogenesis, a morphometric approach was chosen that allows determination of entire thyroid lobes and their constituency, namely the thyroid follicles ( Weber et al, 2015 ). Initial morphological assessment revealed no significant differences in tissue morphology and follicle areas of either age, namely young and older adult mice or genotype, taar1 -/- mice and WT controls ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“… Morphometry of thyroid lobes revealing no gross alteration upon Taar1 deficiency. Cryosections through thyroid tissue obtained from young or older adult C57BL/6 WT and taar1 -/- mice (A) were analyzed by semi-automated morphometry through a Cell Profiler-based pipeline ( Weber et al, 2015 ). Average follicle area per thyroid mid-section denotes the area covered by the thyroid follicles (B) .…”

Section: Resultsmentioning

confidence: 99%

“… Number of cells per thyroid mid-section declines upon Taar1 deficiency, consistent with a higher cell death rate in Taar1-deficient follicles. Cryosections through thyroid tissue obtained from young or older adult C57BL/6 WT and taar1 -/- mice were analyzed by semi-automated morphometry through a Cell Profiler-based pipeline ( Weber et al, 2015 ). The number of cells is given per 1,000 μm 2 area of thyroid mid-section (average counts ± SD) in (A) .…”

Section: Resultsmentioning

confidence: 99%

“…The number of biological replicas used for analyses of cystatin C ( Figures 9B – D ), luminal cystatin D staining intensities ( Figures 9E – G ), anti-Mct8 and anti-Tshr localizations ( Figure 11 ) were n = 3, respectively, for each genotype and age group. The epithelial extensions (EExts), follicle areas, follicle counts, follicle luminal areas, cell numbers per 1,000 μm 2 of tissue area, as well as the fluorescence intensities of anti-cystatin C- and D-, anti-Tg, and ConA-positive signals were analyzed with the aid of the open source software Cell Profiler (version 2.1.1.; available from the Broad Institute at www.cellprofiler.org , Lamprecht et al, 2007 ), following our established pipelines described elsewhere ( Weber et al, 2015 ). For determination of EExts ( Figure 3A ), analyses of follicle areas ( Figure 1B ), and determination of cell counts per follicle area ( Figure 2A ), the number of biological replicas analyzed was n = 4, 4, 4, and 3 for young WT, young taar1 -/- , older adult WT, and older adult taar1 -/- , respectively, with 208, 270, 275, and 200 total number of technical replicas, i.e., follicles, per experimental group, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Canonical TSH Regulation of Cathepsin-Mediated Thyroglobulin Processing in the Thyroid Gland of Male Mice Requires Taar1 Expression

et al. 2018

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Trace amine-associated receptor 1 (Taar1) has been suggested as putative receptor of thyronamines. These are aminergic messengers with potential metabolic and neurological effects countering their contingent precursors, the thyroid hormones (THs). Recently, we found Taar1 to be localized at the primary cilia of rodent thyroid epithelial cells in vitro and in situ. Thus, Taar1 is present in a location of thyroid follicles where it might be involved in regulation of cathepsin-mediated proteolytic processing of thyroglobulin, and consequently TH synthesis. In this study, taar1 knock-out male mice (taar1-/-) were used to determine whether Taar1 function would entail differential alterations in thyroid states of young and adult animals. Analyses of blood serum revealed unaltered T4 and T3 concentrations and unaltered T3-over-T4 ratios upon Taar1 deficiency accompanied, however, by elevated TSH concentrations. Interestingly, TSH receptors, typically localized at the basolateral plasma membrane domain of wild type controls, were located at vesicular membranes in thyrocytes of taar1-/- mice. In addition, determination of epithelial extensions in taar1-/- thyroids showed prismatic cells, which might indicate activation states higher than in the wild type. While gross degradation of thyroglobulin was comparable to controls, deregulated thyroglobulin turnover in taar1-/- mice was indicated by luminal accumulation of covalently cross-linked thyroglobulin storage forms. These findings were in line with decreased proteolytic activities of thyroglobulin-solubilizing and -processing proteases, due to upregulated cystatins acting as their endogenous inhibitors in situ. In conclusion, Taar1-deficient mice are hyperthyrotropinemic in the absence of respective signs of primary hypothyroidism such as changes in body weight or TH concentrations in blood serum. Thyrocytes of taar1-/- mice are characterized by non-canonical TSH receptor localization in intracellular compartments, which is accompanied by altered thyroglobulin turnover due to a disbalanced proteolytic network. These finding are of significance considering the rising popularity of using TAAR1 agonists or antagonists as neuromodulating pharmacological drugs. Our study highlights the importance of further evaluating potential off-target effects regarding TSH receptor mislocalization and the thyroglobulin processing machinery, which may not only affect the TH-generating thyroid gland, but may emanate to other TH target organs like the CNS dependent on their proper supply.

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Functional analysis of the angio-follicular unit of the mouse thyroid gland

Cited by 2 publications

References 0 publications

Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism

Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism

Canonical TSH Regulation of Cathepsin-Mediated Thyroglobulin Processing in the Thyroid Gland of Male Mice Requires Taar1 Expression

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