Role of thyroid peroxidase in health and disease: A comprehensive update on TPO gene and protein expression, enzymatic activity and pharmacological modulation

Thyroid peroxidase (TPO) is a crucial enzyme in thyroid hormone (TH) biosynthesis, catalyzing iodination and coupling reactions for triiodothyronine (T3) and thyroxine (T4) production. In addition to the known enzymatic inhibition mediated by some compounds, increasing evidence indicates that various drugs can modulate TPO mRNA and/or protein expression (e.g., protein kinase activators, cytokines, epigenetic drugs). This review comprehensively explores current evidence on the pharmacological regulation of TPO expression, encompassing its molecular structure, enzymatic function, and involvement in physiological and pathological conditions (e.g., thyroid cancer, autoimmune thyroid diseases, congenital hypothyroidism and hyperthyroidism). Among compounds reported to affect TPO expression, the antithyroid drugs (ATDs) methimazole (MMI) and propylthiouracil (PTU) show variable effects across in vitro and in vivo models, yielding heterogeneous and sometimes conflicting results. Considering that ATDs are the only class of drugs known to directly target TPO and the current lack of works gathering all the related information, there is a need for clarifying ATD-mediated modulation of TPO expression. A systematic PubMed search identified 437 records, of which 22 original studies met inclusion criteria in this work. Overall, available data suggest time-, dose-, and species-dependent ATD effects on TPO expression, highlighting the need for further research to determine clinical relevance.