L-Thyroxine

L-Thyroxine is a synthetic thyroid hormone that mimics the natural thyroxine secreted by the thyroid gland and plays a crucial role in regulating metabolism and promoting growth and development^[1]. L-Thyroxine is commonly used to treat hypothyroidism and other thyroid-related diseases^[2]. Additionally, L-Thyroxine is used in diagnostic tests for thyroid function^[3] and has been shown to protect myocardial function^[4].

In vitro, treatment of U2OS and MG63 osteoblast-like cells with L-Thyroxine (2.5–10μM) for 1 hour significantly increased the expression of Angiopoietin-1 (Ang1) in a dose-dependent manner. L-Thyroxine also significantly enhanced alkaline phosphatase (ALP) activity and cell mineralization capacity. Moreover, it significantly upregulated the expression of osteoblast-related protein markers, such as COL1A1, OC, BSP, Dlx5, Runx2, and OSX^[5]. When human bronchial smooth muscle cells (ASM) were treated with L-Thyroxine (1–100nM) in combination with TGF-β1 (2ng/ml) for 28 hours, L-Thyroxine (100nM) significantly enhanced the proliferative response of ASM cells and reduced the expression of contractile proteins induced by TGF-β1 ^[6].

In vivo, L-Thyroxine (1μg/kg) was administered subcutaneously to mice, which were then exposed to gamma radiation (6Gy) or intraperitoneally injected with cisplatin (15mg/kg) to induce nephrotoxicity. L-Thyroxine significantly improved elevated renal function biomarkers, oxidative stress, and protected renal tissue from subsequent cellular damage^[7]. In Ames dwarf mice, L-Thyroxine (0.1μg/g) in combination with growth hormone (GH, 6μg/g) was administered via subcutaneous injection twice a week starting at 2 weeks of age for 6 weeks. This treatment significantly promoted the growth of Ames dwarf mice^[8].

References:
[1] Darbinyan L, Simonyan K, Hambardzumyan L, et al. Impact of L-thyroxine on hippocampal activity, morphology, and behavioral performance in thyroidectomized rats. Metab Brain Dis. 2025 Mar 10;40(3):140.
[2] McDermott MT. Hypothyroidism. Ann Intern Med. 2020 Jul 7;173(1):ITC1-ITC16.
[3] Fugazzola L, Persani L, Mannavola D, et al. Recombinant human TSH testing is a valuable tool for differential diagnosis of congenital hypothyroidism during L-thyroxine replacement. Clin Endocrinol (Oxf). 2003 Aug;59(2):230-6.
[4] Wang Y, Zhu S, Liu H, et al. Thyroxine Alleviates Energy Failure, Prevents Myocardial Cell Apoptosis, and Protects against Doxorubicin-Induced Cardiac Injury and Cardiac Dysfunction via the LKB1/AMPK/mTOR Axis in Mice. Dis Markers. 2019 Dec 16;2019:7420196.
[5] Park SH, Lee J, Kang MA, et al. Potential of l-thyroxine to differentiate osteoblast-like cells via Angiopoietin1. Biochem Biophys Res Commun. 2016 Sep 23;478(3):1409-15.
[6] Dekkers BG, Naeimi S, Bos IS, et al. L-thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1. Am J Physiol Lung Cell Mol Physiol. 2015 Feb 1;308(3):L301-6.
[7] El-Hamoly T, El-Sharawy DM, El Refaye MS, et al. L-thyroxine modifies nephrotoxicity by regulating the apoptotic pathway: The possible role of CD38/ADP-ribosyl cyclase-mediated calcium mobilization. PLoS One. 2017 Sep 11;12(9):e0184157.
[8] Do A, Menon V, Zhi X, Gesing A, et al. Thyroxine modifies the effects of growth hormone in Ames dwarf mice. Aging (Albany NY). 2015 Apr;7(4):241-55.

L-Thyroxine是一种合成甲状腺激素，可模拟甲状腺分泌的天然甲状腺素，对调节新陈代谢、促进生长发育等起着关键作用^[1]。L-Thyroxine常用于治疗甲状腺功能减退症及其他甲状腺相关疾病^[2]。此外，L-Thyroxine也用于甲状腺功能的诊断检测^[3]，还具备保护心肌功能的作用^[4]。

在体外，L-Thyroxine（2.5–10μM）处理U2OS和MG63成骨细胞样细胞1小时，可显著增加Angiopoietin-1（Ang1）的表达，并呈剂量依赖性；同时，L-Thyroxine显著提高碱性磷酸酶（ALP）活性，增强细胞矿化能力，此外，L-Thyroxine还显著上调了成骨相关蛋白标志物（如COL1A1、OC、BSP、Dlx5、Runx2和OSX）的表达^[5]。L-Thyroxine（1–100nM）与TGF-β1（2ng/ml）联合处理处理人支气管平滑肌细胞（ASM）28小时，L-Thyroxine（100nM）显著增强ASM细胞的增殖反应，同时减少TGF-β1诱导的收缩蛋白的表达 ^[6]。

在体内，L-Thyroxine（1μg/kg）皮下注射预处理小鼠，随后暴露于γ射线（6Gy）或腹腔注射顺铂（15mg/kg）诱导肾毒性，L-Thyroxine显著改善了升高的肾功能生物标志物、氧化应激，并保护肾脏组织免受随后的细胞损伤^[7]。L-Thyroxine（0.1μg/g）与生长激素（GH，6μg/g）联合治疗Ames dwarf mice，从2周龄开始，每周两次皮下注射，持续6周，用于处理Ames矮小鼠。L-Thyroxine显著促进了Ames dwarf mice的生长^[8]。