Nancy Schanze1,2, Simon Friedrich Jacobi2,3, Eddy Rijntjes1, Stefan Mergler4, Marta Del Olmo1, Carolin Stephanie Hoefig1,2, Noushafarin Khajavi3, Ina Lehmphul1, Heike Biebermann3, Jens Mittag2,5, Josef Köhrle1. 1. 1 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany . 2. 2 Department of Cell and Molecular Biology, Karolinska Institutet , Stockholm, Sweden . 3. 3 Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany . 4. 4 Experimentelle Ophthalmologie, Charité-Universitätsmedizin Berlin , Berlin, Germany . 5. 5 Molecular Endocrinology, Universitätsklinikum Schleswig-Holstein , Medizinische Klinik I/CBBM, Lübeck, Germany .
Abstract
BACKGROUND: 3-Iodothyronamine (3-T1AM) is an endogenous decarboxylated thyroid hormone (TH) metabolite. Pharmacological doses of 3-T1AM decrease heart rate, body temperature, and metabolic rate in rodents-effects that are contrary to classic TH excess. Furthermore, a single dose of 3-T1AM was shown to suppress the hypothalamic-pituitary-thyroid (HPT) axis in rats. It was hypothesized that 3-T1AM might play a role in the fine-tuning of TH action and might have a direct regulatory effect on the thyroid gland. METHODS: This study tested whether repeated 3-T1AM treatment interfered with thyroid function and the HPT axis in mice. Therefore, male C57BL/6 mice were intraperitoneally injected with 5 mg/kg of 3-T1AM or vehicle daily for seven days. Additionally, the effects of 3-T1AM on the differentiated rat thyrocyte cell line PCCL3 were analyzed. RESULTS: Repeated administration of 3-T1AM decreased thyroidal mRNA content of the sodium iodide symporter (Nis), thyroglobulin, and pendrin in mice. No interference with the HPT axis was observed, as determined by unaltered pituitary mRNA levels of triiodothyronine-responsive genes, including thyrotropin subunit β. Furthermore, 3-T1AM treatment did not change transcript levels of hepatic triiodothyronine-responsive genes, such as deiodinase 1. In line with this, serum TH concentrations were not changed after the treatment period of seven days. In concordance with the in vivo findings, 3-T1AM decreased the thyrotropin-dependent expression of Nis and functional iodide uptake in PCCL3 cells in vitro. Additionally, uptake and metabolism of 3-T1AM by PCCL3 cells was observed, as well as 3-T1AM-dependent changes in intracellular Ca2+ concentration that might be involved in mediating the reported effects. CONCLUSIONS: In conclusion, 3-T1AM application decreased expression of selected TH synthesis genes by acting directly on the thyroid gland, and it might therefore affect TH synthesis without involvement of the HPT axis.
BACKGROUND:3-Iodothyronamine (3-T1AM) is an endogenous decarboxylated thyroid hormone (TH) metabolite. Pharmacological doses of 3-T1AM decrease heart rate, body temperature, and metabolic rate in rodents-effects that are contrary to classic TH excess. Furthermore, a single dose of 3-T1AM was shown to suppress the hypothalamic-pituitary-thyroid (HPT) axis in rats. It was hypothesized that 3-T1AM might play a role in the fine-tuning of TH action and might have a direct regulatory effect on the thyroid gland. METHODS: This study tested whether repeated 3-T1AM treatment interfered with thyroid function and the HPT axis in mice. Therefore, male C57BL/6 mice were intraperitoneally injected with 5 mg/kg of 3-T1AM or vehicle daily for seven days. Additionally, the effects of 3-T1AM on the differentiated rat thyrocyte cell line PCCL3 were analyzed. RESULTS: Repeated administration of 3-T1AM decreased thyroidal mRNA content of the sodium iodide symporter (Nis), thyroglobulin, and pendrin in mice. No interference with the HPT axis was observed, as determined by unaltered pituitary mRNA levels of triiodothyronine-responsive genes, including thyrotropin subunit β. Furthermore, 3-T1AM treatment did not change transcript levels of hepatic triiodothyronine-responsive genes, such as deiodinase 1. In line with this, serum TH concentrations were not changed after the treatment period of seven days. In concordance with the in vivo findings, 3-T1AM decreased the thyrotropin-dependent expression of Nis and functional iodide uptake in PCCL3 cells in vitro. Additionally, uptake and metabolism of 3-T1AM by PCCL3 cells was observed, as well as 3-T1AM-dependent changes in intracellular Ca2+ concentration that might be involved in mediating the reported effects. CONCLUSIONS: In conclusion, 3-T1AM application decreased expression of selected TH synthesis genes by acting directly on the thyroid gland, and it might therefore affect TH synthesis without involvement of the HPT axis.
Authors: Keith H Richards; Nancy Schanze; Ray Monk; Eddy Rijntjes; Daniel Rathmann; Josef Köhrle Journal: PLoS One Date: 2017-08-24 Impact factor: 3.240
Authors: Ersal Türker; Fabian Garreis; Noushafarin Khajavi; Peter S Reinach; Pooja Joshi; Tobias Brockmann; Alexander Lucius; Nina Ljubojevic; Elizabeth Turan; Drew Cooper; Felix Schick; Rob Reinholz; Uwe Pleyer; Josef Köhrle; Stefan Mergler Journal: Front Endocrinol (Lausanne) Date: 2018-11-22 Impact factor: 5.555
Authors: Lia Walcher; Clara Budde; Arina Böhm; Peter S Reinach; Priyavathi Dhandapani; Nina Ljubojevic; Markus W Schweiger; Henriette von der Waydbrink; Ilka Reimers; Josef Köhrle; Stefan Mergler Journal: Front Pharmacol Date: 2018-11-13 Impact factor: 5.810