Mechanisms underlying disruptive effects of pesticides on the thyroid function

The regulation of thyroid hormones (THs) production and physiological action is complex and can be adversely disrupted by a broad spectrum of chemicals at environmentally relevant concentrations through different and intricate mechanisms. This study reviews the current knowledge on how chemicals, in particular pesticides, can disrupt TH homeostasis. These include a) inhibition of TH biosynthesis in the thyroid follicular cells resulting in perturbation of the hypothalamic-pituitary-thyroid (HPT) axis; b) interference with TH transport proteins in the bloodstream; c) liver enzyme induction leading to increased inactivation and further excretion of TH from the body; d) interference with conversion of TH into the active form in peripheral tissues; e) interference with the transport of TH through cell membranes; and f) binding to intracellular TH receptors and further dysregulation of downstream gene expression sensitive to TH. Most pesticides included in the cumulative assessment group "hypothyroidism" by EFSA affect the HPT axis through upregulation of TH elimination pathways. A better understanding of the molecular mechanism behind the adverse effects, or at least the mode of action of each pesticide, reduces the uncertainty when the combined risk of dietary exposure to pesticides is assessed according to the dose-addition model.