title: 3-Iodothyronamine Decreases Expression of Genes Involved in Iodide Metabolism in Mouse Thyroids and Inhibits Iodide Uptake in PCCL3 Thyrocytes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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: 1 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .|2 Department of Cell and Molecular Biology, Karolinska Institutet , Stockholm, Sweden .
authors: Nancy
authors: N
authors: Schanze
authors: 2 Department of Cell and Molecular Biology, Karolinska Institutet , Stockholm, Sweden .|3 Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors: Simon Friedrich
authors: SF
authors: Jacobi
authors: 1 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors: Eddy
authors: E
authors: Rijntjes
authors: 4 Experimentelle Ophthalmologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors: Stefan
authors: S
authors: Mergler
authors: 1 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors: Marta
authors: M
authors: Del Olmo
authors: 1 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .|2 Department of Cell and Molecular Biology, Karolinska Institutet , Stockholm, Sweden .
authors: Carolin Stephanie
authors: CS
authors: Hoefig
authors: 3 Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors: Noushafarin
authors: N
authors: Khajavi
authors: 1 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors: Ina
authors: I
authors: Lehmphul
authors: 3 Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors: Heike
authors: H
authors: Biebermann
authors: 2 Department of Cell and Molecular Biology, Karolinska Institutet , Stockholm, Sweden .|5 Molecular Endocrinology, Universitätsklinikum Schleswig-Holstein , Medizinische Klinik I/CBBM, Lübeck, Germany .
authors: Jens
authors: J
authors: Mittag
authors: 1 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors: Josef
authors: J
authors: Köhrle
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects*; D007454:Iodides / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000076988:Sulfate Transporters; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D013954:Thyroglobulin / Q000235:genetics / Q000378:metabolism; D000072637:Thyroid Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013970:Thyronines / Q000494:pharmacology*; D000099209:Sodium-Iodide Symporters
chemical_list: D027321:Anion Transport Proteins; D007454:Iodides; D000076988:Sulfate Transporters; D027981:Symporters; D013954:Thyroglobulin; D013970:Thyronines; D000099209:Sodium-Iodide Symporters; C487948:3-iodothyronamine; C494849:Slc26a4 protein, mouse
keywords: 3-iodothyroacetic acid; 3-iodothyronamine; Nis; thyrocytes; thyroid hormone; thyronamine