Mechanistic pathways of developmental interference of endocrine disrupting chemicals with the thyroid hormone system - a narrative review

The thyroid hormone (TH) system of humans, aquatic and terrestrial life forms is a major target for endocrine disrupting chemicals (EDC) during development and adult life. EDC adversely interfere with TH biosynthesis in vascularized thyroid follicles, secretion and distribution to target organs. EDC exposure may affect TH transmembrane transport, intracellular (in-)activation by deiodinases and conjugation reactions as well as T3 binding to intracellular T3 receptors in target cells. Predominant EDC interferences occur with TH distribution in the circulation and with cellular reactions controlling local availability of the active hormone T3 at the pre-receptor level. Developmental EDC interference may irreversible alter setpoints of the feedback regulation of the hypothalamus-pituitary-thyroid axis, TH-dependent brain development, and metabolic functions in adults. The worldwide still prevailing inadequate iodide status, especially during pregnancy and lactation, might exacerbate adverse effects of an increasing spectrum of identified and suspected EDC and their mixtures on human and environmental health. • EDC interfere with TH binding to distributor proteins in the blood, with cellular THTMTs, intracellular DIOs and conjugating enzymes, hereby disturbing pre-receptor control of T3 ligand availability for TRs. • NIS and TPO are main targets of EDC interference with thyroidal TH biosynthesis. • Adversity of EDC actions appears to be increased under conditions of the still prevailing maternal iodide deficiency, especially during pregnancy and lactation.