Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland and promotes thyroid growth and function, with increased TSH levels typically associated with hypothyroidism. Immunohistochemical analysis revealed predominantly nuclei peri-nuclei localization of TSHR in cancerous tissues but cell membrane localization in non-cancerous parts. Overexpression of TSHR was found in a great majority of HCC tissues and associated with unfavorable prognosis.
Thyroid hormone receptor beta (THRB), also known as TRbeta and NR1A2, belongs to the nuclear hormone receptor family. Featuring an N-terminal transactivation domain, a central DNA-binding domain, and a hormone ligand-binding domain, THRB isoform 1 2 expression localizes predominately to the liver and pituitary, respectively. THRB regulates the feedback of T3-dependent thyrotropin-stimulating hormone (TSH) transcription in the pituitary by binding to thyroid hormone (TH) response elements present on promoters of TH-responsive genes. Located on chromosome 3p24, THRB gene mutation has been linked to autosomal dominant resistance to TH (RTH), which is characterized by goiter and elevated levels of T3, T4, and TSH. THRB is a known pharmacological target for the treatment of non-alcoholic steatohepatitis (NASH). THRB may be a target for future cancer therapies since its knockdown enhanced the viability of endometrial cancer cells and activated the mTOR-4EBP1 eIF4G pathway.