Harder Lisbeth, Schanze Nancy, Sarsenbayeva Assel, Kugel Franziska, Köhrle Josef, Schomburg Lutz, Mittag Jens, Hoefig Carolin S
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Center of Brain, Behavior and Metabolism (CBBM)/Medizinische Klinik I, University of Lübeck, Lübeck, Germany.
Eur Thyroid J. 2018 Jan;7(1):3-12. doi: 10.1159/000481856. Epub 2017 Dec 5.
Thyronamines are decarboxylated and deiodinated metabolites of thyroid hormones (THs). Of all possible thyronamine variants, only 3-iodothyronamine (3-TAM) and iodine-free thyronamine (TAM) have been detected in vivo. While intensive research has been done on the (patho-)physiological action of 3-TAM, the role of TAM has been studied less intensively.
We determined whether a single pharmacological dose (50 mg/kg, i.p.) or repeated administration (5 mg/kg/day, i.p., for 7 days) of TAM affects metabolism, cardiovascular function, or thermoregulation in male C57BL/6J mice. Since selenium (Se) is important for proper TH function and Se metabolism is affected by TH, we additionally analyzed Se concentrations in liver, serum, and kidney using total reflection X-ray analysis.
A single injection of TAM had no effect on heart rate, temperature, or activity as assessed by radio telemetry. Likewise, daily administration of TAM did not alter body weight, food or water intake, heart rate, blood pressure, brown adipose tissue thermogenesis, or body temperature, and no significant differences in hepatic glycogen content or mRNA expression of genes involved in cardiovascular function or metabolic control were determined. Also, the X-ray analysis of Se concentrations revealed no significant changes. However, hepatic TAM was significantly increased in the treated animals.
In summary, our data demonstrate that TAM elicits no obvious metabolic, cardiovascular, or thermoregulatory activities in mice. As TAM does also not interfere with TH or Se metabolism, we conclude that the deiodination of 3-TAM to TAM constitutes an efficient inactivation mechanism, terminating the actions of the more powerful precursor.
甲状腺胺是甲状腺激素(THs)的脱羧和脱碘代谢产物。在所有可能的甲状腺胺变体中,体内仅检测到3-碘甲状腺胺(3-TAM)和无碘甲状腺胺(TAM)。虽然对3-TAM的(病理)生理作用已进行了深入研究,但对TAM作用的研究较少。
我们确定单次药理剂量(50mg/kg,腹腔注射)或重复给药(5mg/kg/天,腹腔注射,共7天)的TAM是否会影响雄性C57BL/6J小鼠的代谢、心血管功能或体温调节。由于硒(Se)对甲状腺激素的正常功能很重要,且硒代谢受甲状腺激素影响,我们还使用全反射X射线分析来分析肝脏、血清和肾脏中的硒浓度。
通过无线电遥测评估,单次注射TAM对心率、体温或活动没有影响。同样,每日给予TAM也不会改变体重、食物或水的摄入量、心率、血压、棕色脂肪组织产热或体温,并且在肝脏糖原含量或参与心血管功能或代谢控制的基因的mRNA表达方面未确定有显著差异。此外,硒浓度的X射线分析显示没有显著变化。然而,在接受治疗的动物中,肝脏中的TAM显著增加。
总之,我们的数据表明TAM在小鼠中不会引发明显的代谢、心血管或体温调节活动。由于TAM也不干扰甲状腺激素或硒代谢,我们得出结论,3-TAM脱碘生成TAM构成了一种有效的失活机制,可以终止更强大前体的作用。