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.