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These actions depend on provision of thyroid hormones in the circulation but also to a remarkable extent on deiodinase enzymes in target tissues that amplify or deplete the local concentration of the primary active form of the hormone T3 (3,5,3\u2032-triiodothyronine), the high affinity ligand for thyroid hormone receptors. Genetic analyses in mice have revealed key roles for activating (DIO2) and inactivating (DIO3) deiodinases in cell differentiation fates and tissue maturation, ultimately promoting neonatal viability, growth, fertility, brain development, and behavior, as well as metabolic, endocrine, and sensory functions. An emerging paradigm is how the opposing activities of DIO2 and DIO3 are coordinated, providing a dynamic switch that controls the developmental timing of a tissue response, often during neonatal and maturational transitions. A second paradigm is how cell to cell communication within a tissue determines the response to T3. Deiodinases in specific cell types, often strategically located near to blood vessels that convey thyroid hormones into the tissue, can regulate neighboring cell types, suggesting a paracrine-like layer of control of T3 action. We discuss deiodinases as switches for developmental transitions and their potential to influence tissue dysfunction in human thyroid disorders.<\/jats:p>","DOI":"10.1210\/endocr\/bqab091","type":"journal-article","created":{"date-parts":[[2021,5,8]],"date-time":"2021-05-08T17:15:04Z","timestamp":1620494104000},"source":"Crossref","is-referenced-by-count":54,"title":["Thyroid Hormone Deiodinases: Dynamic Switches in Developmental Transitions"],"prefix":"10.1210","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6314-3987","authenticated-orcid":false,"given":"Arturo","family":"Hernandez","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Maine Medical Center Research Institute, Maine Health, Scarborough, Maine 04074, USA"},{"name":"Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111, USA"},{"name":"Graduate School of Biomedical Science and Engineering, University of Maine, Orono, Maine 04469, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Elena","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Maine Medical Center Research Institute, Maine Health, Scarborough, Maine 04074, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Ng","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, Bethesda, Maryland 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3463-4162","authenticated-orcid":false,"given":"Douglas","family":"Forrest","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, Bethesda, Maryland 20892, 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