Exp Clin Endocrinol Diabetes 2015; 123 - P12_10
DOI: 10.1055/s-0035-1547744

Effects of repeated 3-T1AM treatment on thyrocytes in mice

N Schanze 1, S Jacobi 2, C Höfig 3, J Mittag 4, J Köhrle 5
  • 1Institut für Experimentelle Endokrinologie, Charité – Universitätsmedizin Berlin
  • 2Institut für Experimentelle Pädiatrische Endokrinologie, Charité – Universitätsmedizin Berlin
  • 3Karolinska Institutet, Department of Cell & Molecular Biology, Sweden; Institut für Experimentelle Endokrinologie, Charité – Universitätsmedizin Berlin, Germany; Department of Cell & Molecular Biology
  • 4Universität Lübeck; Cbbm/Medi; Mfc1
  • 5Institut für Experimentelle Endokrinologie, Charité – Universitätsmedizin Berlin, Germany; Institut für Experimentelle Endokrinologie

3-T1AM, an endogenous thyroid hormone metabolite, exerts remarkable effects after i.p. injection in mice, e.g. bradycardia, decreased body temperature and cardiac output. Furthermore, 3-T1AM has been reported to interfere with the hypothalamic-pituitary-thyroid (HPT) axis in rats after a single injection of 50 mg/kg, as determined by decreased T4 and TSH plasma concentration. We hypothesize that 3-T1AM might play a role in the fine tuning of thyroid hormone action and might have a direct regulatory effect on the thyroid gland. Therefore, we tested whether repeated low dose treatment with 3-T1AM interfered with thyroid function and the HPT axis in mice.

Male C57BL/6 mice were i.p. injected with either 5 mg/kg 3-T1AM or vehicle for 7 days. Effects on gene expression were analyzed in thyroid gland, liver and pituitary. Serum T4 concentration was measured via ELISA.

Repeated administration of 3-T1AM significantly decreased thyroidal mRNA levels of the Sodium-iodide symporter (NIS), Thyroglobulin and Pendrin in mice. No effects on the HPT axis were observed, as determined by unchanged transcript levels of β-TSH and the T3-responsive genes TRH receptor, TRH degrading enzyme and Dio2 in the pituitary, as well as unaltered serum T4 concentrations. Furthermore, 3-T1AM treatment did not change transcript levels of T3-responsive Dio1 and Spot14 in the liver.

Repeated 3-T1AM treatment decreased gene expression of NIS, Pendrin and Thyroglobulin in thyrocytes in mice without interference with the HPT axis within the treatment period of 7 days. In conclusion, our data indicate a direct action of 3-T1AM on thyroidal gene expression.

(Supported by DFG SPP1629 Thyroid Trans Act TP 16 – 1 and Research Fellowship)