Molecular Functions of Thyroid Hormones and Their Clinical Significance in Liver-Related Diseases

Abstract

Thyroid hormones (THs) are potent mediators of several physiological processes, including embryonic development, cellular differentiation, metabolism, and cell growth. Triiodothyronine (T3) is the most biologically active TH form. Thyroid hormone receptors (TRs) belong to the nuclear receptor superfamily and mediate the biological functions of T3 via transcriptional regulation. TRs generally form heterodimers with the retinoid X receptor (RXR) and regulate target genes upon T3 stimulation. Research over the past few decades has revealed that disruption of cellular TH signaling triggers chronic liver diseases, including alcoholic or nonalcoholic fatty liver disease and hepatocellular carcinoma (HCC). Animal model experiments and epidemiologic studies to date imply close associations between high TH levels and prevention of liver disease. Moreover, several investigations spanning four decades have reported the therapeutic potential of T3 analogs in lowering lipids, preventing chronic liver disease, and as anticancer agents. Thus, elucidating downstream genes/signaling pathways and molecular mechanisms of TH actions is critical for the treatment of significant public health issues. Here, we have reviewed recent studies focusing on the roles of THs and TRs in several disorders, in particular, liver diseases. We also discuss the potential therapeutic applications of THs and underlying molecular mechanisms.

Identification of serum biomarkers associated with hepatitis B virus-related hepatocellular carcinoma and liver cirrhosis using mass-spectrometry-based metabolomics

“…In Asia, hepatitis B virus (HBV) infection is considered the most important cause for HCC, accounting for 80-90 % of HCC cases (Yin et al 2009). The majority (70-80 %) of HBV-related HCC cases occur in patients accompanied with liver cirrhosis; however, HBV can cause HCC even when individuals have not developed formal liver cirrhosis (Chi et al 2013). According to the estimation of the World Yonghai Lu and Chong Huang have contributed equally to this work.…”

Chemotherapy resistance and metastasis-promoting effects of thyroid hormone in hepatocarcinoma cells are mediated by suppression of FoxO1 and Bim pathway

“…5 Liver is one of the major target organs of T 3 , and body TH levels are closely correlated with multiple liver-associated diseases, such as hepatocellular carcinoma (HCC). [6][7][8][9] In the diethylnitrosamine (DEN)-induced HCC animal model, 10,11 T 3 has been identified as a potent inhibitor of HCC development, although significant associated mitogenic effects on hepatocytes are reported. Conversely, in chemotherapyresistant populations of advanced HCC cells, TH/TR has been shown to promote tumor cell metastasis via upregulation of several extracellular matrix (ECM) proteases, such as matrix metalloproteinase (MMP)-2, -7 and -9.…”

Effect of aqueous extract of Murraya koenigii on haematological, hormonal and lipid profile of Albino rats

“…Thyroid hormones play important role in the growth and development of the body and regulate metabolism [34]. So, with an increase in thyroid activity, marked changes in thyroid hormone production, metabolism and action occur.…”