Josef Köhrle

Josef Köhrle
Charité Universitätsmedizin Berlin | Charité · Institute of Experimental Endocrinology

Dr. rer. nat.

About

498
Publications
43,128
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19,572
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Additional affiliations
April 2017 - present
Charité Universitätsmedizin Berlin
Position
  • Managing Director
December 2001 - March 2017
Charité Universitätsmedizin Berlin
Position
  • Manager

Publications

Publications (498)
Article
Full-text available
Background Despite being the most performed laboratory endocrine investigation, the optimum use of thyroid tests (thyrotropin [TSH] and thyroid hormone [TH] measurement) is open to question and the interpretation of the results from these tests can be ambiguous. The American Thyroid Association (ATA) with its expertise support the endeavor of the U...
Article
Full-text available
The energy homeostasis of the organism is orchestrated by a complex interplay of energy substrate shuttling, breakdown, storage, and distribution. Many of these processes are interconnected via the liver. Thyroid hormones (TH) are well known to provide signals for the regulation of energy homeostasis through direct gene regulation via their nuclear...
Article
Full-text available
African mole-rats are subterranean rodents inhabiting underground burrows. This habitat entails risks of overheating, hypoxia, and scarce food availability. Consequently, many subterranean species have evolved low basal metabolism and low body temperature, but the regulation of these traits at the molecular level were unknown. Measurements of serum...
Article
Full-text available
The adequate availability and metabolism of three essential trace elements, iodine, selenium and iron, provide the basic requirements for the function and action of the thyroid hormone system in humans, vertebrate animals and their evolutionary precursors. Selenocysteine-containing proteins convey both cellular protection along with H2O2-dependent...
Article
Iodothyronine deiodinases (DIO) are a family of selenoproteins controlling systemic and local availability of the major thyroid hormone l-thyroxine (T4), a prohormone secreted by the thyroid gland. T4 is activated to the active 3,3’-5-triiodothyronine (T3) by two 5’-deiodinases, DIO1 and DIO2. DIO3, a 5-deiodinase selenoenzyme inactivates both the...
Article
Full-text available
Mice with constitutive disruption of the Selenop gene have been key to delineate the importance of selenoproteins in neurobiology. However, the phenotype of this mouse model is exquisitely dependent on selenium supply and timing of selenium supplementation. Combining biochemical, histological, and behavioral methods, we tested the hypothesis that p...
Article
Full-text available
Thyroid hormones, their metabolites, and synthetic analogues are potential anti-steatotic drug candidates considering that subclinical and manifest hypothyroidism is associated with hepatic lipid accumulation, non-alcoholic fatty liver disease, and its pandemic sequelae. Thyromimetically active compounds stimulate hepatic lipogenesis, fatty acid be...
Article
Full-text available
We examined relationships between thyroid hormone (TH) metabolites in humans by measuring 3,5-diiodothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM) levels after liothyronine administration. In secondary analyses, we measured 3,5-T2 and 3-T1AM concentrations in stored samples from two clinical trials. In 12 healthy volunteers, THs and metabolites...
Preprint
Full-text available
Thyroid hormones, their metabolites and synthetic analogues are potential anti-steatotic drug candidates considering that subclinical and manifest hypothyroidism is associated with hepatic lipid accumulation, non-alcoholic fatty liver disease, and its pandemic sequelae. Thyromimetically active compounds stimulate hepatic lipogenesis, fatty acid bet...
Article
Full-text available
In animal studies, both in basic science and in toxicological assessment of potential endocrine disruptors, the state of the thyroid hormone (TH) axis is often described and defined exclusively by the concentrations of circulating THs and TSH. Although it is known that the local, organ-specific effects of THs are also substantially regulated by loc...
Article
Disruption of the thyroid hormone system during development can impair brain development and cause irreversible damage. Some thyroid hormone system disruptors act by inhibiting the thyroperoxidase (TPO) enzyme, which is key to thyroid hormone synthesis. For the potent TPO-inhibiting drug propylthiouracil (PTU) this has been shown to result in thyro...
Article
Thyroid hormone (TH) metabolism and cellular TH action are influenced by ageing. To investigate response to thyroxine (T4) overtreatment, a kinetic study was conducted in young and aged mice with chronic hyperthyroidism and hormone withdrawal. Five and 22 months old male mice were treated with T4 or PBS over 5 weeks, followed by observation for up...
Article
The thyroid hormone system is a main target of endocrine disruptor compounds (EDC) at all levels of its intricately fine-tuned feedback regulation, synthesis, distribution, metabolism and action of the ‘prohormone’ thyroxine and its active metabolites. Apart from classical antithyroid effects of EDC on the gland, the majority of known and suspected...
Chapter
The thyroid gland, its feedback regulation within the hypothalamus–, pituitary–, thyroid–periphery axis, and the action of thyroid hormones belong to the most vulnerable components of the endocrine system affected by our environment. Thyroid hormone synthesis critically depends on live long nutritional availability of three essential trace elements...
Article
The thyroperoxidase (TPO) enzyme is expressed by the thyroid follicular cells and is required for thyroid hormone synthesis. In turn, thyroid hormones are essential for brain development, thus inhibition of TPO in early life can have life-long consequences for brain function. If environmental chemicals with the capacity to inhibit TPO in vitro can...
Article
Full-text available
Endocrine Connections was launched by the European Society of Endocrinology (ESE) and the Society for Endocrinology (SfE) with two issues in 2012. It was the first open access journal devoted entirely to the research of hormones.
Article
Aims Obesity is an increasing problem, even in young women of reproductive age. Obesity has a negative impact on conception, the course of pregnancy, and neonatal outcomes. Caring for obese pregnant women is becoming an increasingly important aspect of standard prenatal care. This guideline aims to improve the care offered to obese pregnant women....
Article
Background: The thyroid hormone (TH) metabolite 3,5-diiodothyronine (3,5-T2) is considered as a potential drug for treatment of non-alcoholic fatty liver disease (NAFLD) based on its prominent anti-steatotic effects in murine models of obesity without the detrimental thyromimetic side effects known for classical TH. To expand our understanding of...
Article
Selenium (Se), apart from iodine, iron, and calcium, is one of the nutrient-derived key elements strongly affecting the endocrine system. However, no specific hormonal “feedback” regulation for Se status has yet been identified, in contrast to the fine-tuned hormone network regulating Ca2+ and phosphate balance or hepcidin-related iron status. Sinc...
Article
The European Society of Toxicologic Pathology organized an expert workshop in May 2018 to address adversity considerations related to thyroid follicular cell hypertrophy and/or hyperplasia (FCHH), which is a common finding in nonclinical toxicity studies that can have important implications for risk assessment of pharmaceuticals, food additives, an...
Article
Background: Pathological conditions of the thyroid hormone (TH) system are routinely diagnosed using serum concentrations of thyroid-stimulating hormone (TSH), which is sufficient in most cases. However, in certain conditions, such as resistance to TH due to mutations in THRB (RTHb) or TSH-releasing pituitary adenoma (TSHoma), TSH may be insuffici...
Article
Full-text available
The wide spectrum of novel applications for the LC-MS/MS-based analysis of thyroid hormone metabolites (THM) in blood samples and other biological specimen highlights the perspectives of this novel technology. However, thorough development of pre-analytical sample workup and careful validation of both pre-analytics and LC-MS/MS analytics, is needed...
Article
Thyroid hormones (TH) are key regulators of bone health, and TH excess in mice causes high bone turnover‐mediated bone loss. However, the underlying molecular mechanisms of TH actions on bone remain poorly defined. Here, we tested the hypothesis whether TH mediate their effects via the pro‐osteogenic bone morphogenetic protein (BMP) signaling pathw...
Article
Thyroid hormone metabolites (THM) with few or no iodine substituents such as 3,5-T2, the thyronamines 3-T1AM and T0AM, and their oxidation products, the thyroacetic acids (TA) formed by monoamine oxidases, have recently attracted major interest due to their metabolic actions which are in part distinct from those of the classical thyromimetic hormon...
Article
Full-text available
The test methods that currently exist for the identification of thyroid hormone system-disrupting chemicals are woefully inadequate. There are currently no internationally validated in vitro assays, and test methods that can capture the consequences of diminished or enhanced thyroid hormone action on the developing brain are missing entirely. These...
Article
Full-text available
Over the last decades, thyroid hormone metabolites (THMs) received marked attention as it has been demonstrated that they are bioactive compounds. Their concentrations were determined by immunoassay or mass-spectrometry methods. Among those metabolites, 3,5-diiodothyronine (3,5-T2), occurs at low nanomolar concentrations in human serum, but might r...
Article
Background: Bone is an important target of thyroid hormones (THs), which require transport into target cells to exert their actions. Recently, the TH-specific monocarboxylate transporter 8 (Mct8) was reported as a regulator of bone mass in male mice. However, its global deletion leads to high 3,3',5-L-triiodothyronine (T3) serum concentrations that...
Article
Full-text available
Background: In numerous studies based predominantly on rodent models, administration of 3,5-diiodo-L-thyronine (3,5-T2), a metabolite of the thyroid hormones (TH) thyroxine (T4) and triiodo-L-thyronine (T3), was reported to cause beneficial health effects, including reversal of steatohepatosis and prevention of insulin resistance, in most instances...
Article
We report here a novel approach for the extraction and analysis of thyroid hormones (TH) and their metabolites (THM) from human serum samples. Our method features a compact, 96-well micro-titre plate-based pre-analytic extraction/clean-up workflow combined with an isotope dilution LC-MS/MS-MS³ analytical method. In particular, these features make p...
Article
Since the discovery of L-thyroxine, the main secretory product of the thyroid gland, and its major metabolite T3, which exerts the majority of thyroid hormone action via ligand-dependent modulation of the function of T3 receptors in nuclei, mitochondria, and other subcellular compartments, various other T4-derived endogenous metabolites have been i...
Article
We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene express...
Article
Clinical manifestation of hyperthyroidism and hypothyroidism vary with age, with an attenuated, oligosymptomatic presentation of thyroid dysfunction (TD) in older patients. We asked, whether in rodents TD phenotypes are influenced by age and whether this involves changes in systemic and/or organ thyroid hormone (TH) signaling. Chronic hyper- or hyp...
Article
Thyroid hormones regulate bone homeostasis, and exogenously induced hyperthyroidism and hypothyroidism in mice was recently found to be associated with an altered expression of the Wnt inhibitor Dickkopf-1 (Dkk1), a determinant of bone mass. Here, we assessed the role of Dkk1 in thyroid hormone-induced changes in bone using conditional Dkk1 knockou...
Article
The re-discovery of the group of thyronamines (TAM), especially the first detailed description of their most prominent congener 3-iodothyronamine (3T1AM) fourteen years ago boosted research on this thyroid hormone metabolite tremendously. TAM exert actions partly opposite to and distinct from known functions of thyroid hormones. These fascinating m...
Article
Full-text available
This study was undertaken to determine if crosstalk among the transient receptor potential (TRP) melastatin 8 (TRPM8), TRP vanilloid 1 (TRPV1), and vascular endothelial growth factor (VEGF) receptor triad modulates VEGF-induced Ca 2+ signaling in human corneal keratocytes. Using RT-PCR, qPCR and immunohistochemistry, we determined TRPV1 and TRPM8 g...
Article
Full-text available
Background: The health benefits of soy are widely reported but there are queries on the effect of soy isoflavones on thyroid function and the underlying mechanism of action. Materials and Methods: We examined the effect of soy isoflavones on reverse tri-iodothyronine (or 3,3′,5′-tri-iodothyronine; rT3) in two studies comprising 400 patients: 200 me...
Article
Full-text available
In human uveal melanoma (UM), tumor enlargement is associated with increases in aqueous humor vascular endothelial growth factor-A (VEGF-A) content that induce neovascularization. 3-Iodothyronamine (3-T1AM), an endogenous thyroid hormone metabolite, activates TRP melastatin 8 (TRPM8), which blunts TRP vanilloid 1 (TRPV1) activation by capsaicin (CA...
Article
Thyroid hormone metabolites might affect the heart. The endogenous aminergic metabolite 3-Iodothyronamine (T1AM) reduces Left Ventricular Ejection Fraction (LVEF) in rodents. Objective To investigate concentration of T1AM and its association with LVEF and biomarkers of heart function in chronic heart failure (CHF) patients without thyroid disease,...
Article
Abstract Thyroid hormone (TH) and TH receptors (TRs) α and β act by binding to TH response elements (TREs) in regulatory regions of target genes. This nuclear signaling is established as the canonical or type 1 pathway for TH action. Nevertheless, TRs also rapidly activate intracellular second-messenger signaling pathways independently of gene exp...
Article
Full-text available
Isoflavones are secondary plant constituents of certain foods and feeds such as soy, linseeds, and red clover. Furthermore, isoflavone-containing preparations are marketed as food supplements and so-called dietary food for special medical purposes to alleviate health complaints of peri- and postmenopausal women. Based on the bioactivity of isoflavo...
Chapter
More than a century after the discovery of L-Thyroxine, the main thyroid hormone secreted solely by the thyroid gland, several metabolites of this iodinated, tyrosine-derived ancestral hormone have been identified. These are utilized as hormones during development, differentiation, metamorphosis, and regulation of most biochemical reactions in vert...
Article
Full-text available
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 vi...
Article
Micronutrients are essential to health at every life stage and their deficiencies are associated with increased incidence of various pathophysiological states and poor quality of life. Efficient methods are therefore needed to monitor micronutrient status of individuals and to improve evidenced-based recommendations for populations. This review (i)...
Article
Full-text available
Type 1 iodothyronine deiodinase (DIO1) contributes to deiodination of 3,5,3’,5’-tetraiodo-L-thyronine (thyroxine, T4) yielding of 3,5,3’-triiodothyronine (T3), a powerful regulator of cell differentiation, proliferation, and metabolism. Our previous work showed that loss of DIO1 enhances proliferation and migration of renal cancer cells. However, t...
Data
Results of enrichment analysis performed using http://geneontology.org/ platform and PANTHER Overrepresentation Test (release 20160715). (XLSX)
Data
The expression of DIO1 in renal cancer. The plots show results of qPCR analysis performed in 30 matched pairs of tumor (TUMOR) and control (CONTROL) tissue samples. Statistical analysis was performed using Wilcoxon matched pairs signed test. **** p<0.0001. (TIF)
Data
Expression of DIO1 protein in KIJ265T and KIJ308T cells following stable transfection with pcDNA3-DIO1 (DIO1+) or empty plasmid (DIO1-). 60 μg of protein was resolved on SDS-PAGE, β-actin was used as loading control. (TIF)
Data
The expression of DIO1-affected genes in KIJ308T-DIO1(+) and KIJ308T-DIO1(-) cells. The plots show mean ± SEM results of qPCR analysis performed in three independent biological experiments. Statistical analysis was performed using t-test. *p<0.05, **p<0.01. Induction of DIO1 expression in KIJ308T cells is shown in Supplementary S1 Fig. (TIF)
Data
The expression of DIO1-affected genes stratified by risk groups. The data was retrieved from TCGA and the analysis was performed using SurvExpress; t-test was used to compute p values. p<0.05 was considered statistically significant. P values are shown above box plots for each gene. Green: expression in low risk group. Red: expression in high risk...
Data
Matrix of correlations between the expressions of proteins affected by DIO1 expression in renal cancer cells. The analysis was performed using GraphPad Prism 5.0. Pearson correlation coefficients were calculated on log2 normalized data. (XLSX)
Data
NRF2-targets affected by DIO1 expression. ND: no data. (DOC)
Data
Additional information on proteins of which expression was affected by DIO1 in renal cancer cells. (DOCX)
Article
Full-text available
Significance This study changes our understanding of how thyroid hormone acts. Thyroid hormone receptors are considered typical nuclear receptors that bind to DNA and, after binding, alter the expression of their target genes and regulate physiological responses. Nevertheless, we show that thyroid hormone still mediates important physiological effe...
Article
Full-text available
Insulin-resistance is the main cause of type 2 diabetes. Here we describe the identification and characterization of BMP2 and BMP6 as new insulin-sensitizing growth factors in mature adipocytes. We show that BMP2 and BMP6 lead to enhanced insulin-mediated glucose uptake in both insulin-sensitive and -insensitive adipocytes. We exclude a direct effe...
Article
Objectives: Thyronamines are decarboxylated and deiodinated metabolites of thyroid hormones (THs). Of all possible thyronamine variants, only 3-iodothyronamine (3-T1AM) and iodine-free thyronamine (T0AM) have been detected in vivo. While intensive research has been done on the (patho-)physiological action of 3-T1AM, the role of T0AM has been studi...
Article
Full-text available
Selenoprotein biosynthesis relies on the co-translational insertion of selenocysteine in response to UGA codons. Aminoglycoside antibiotics interfere with ribosomal function and may cause codon misreading. We hypothesized that biosynthesis of the selenium (Se) transporter selenoprotein P (SELENOP) is particularly sensitive to antibiotics due to its...
Article
Full-text available
Background: Sex and age play a role in the prevalence of thyroid dysfunction (TD), but their interrelationship for manifestation of hyper- and hypothyroidism is still not well understood. Using a murine model, we asked whether sex impacts the phenotypes of hyper- and hypothyroidism at two life stages. Methods: Hyper- and hypothyroidism were indu...