The cell biology of the thyroid-disrupting mechanism of dichlorodiphenyltrichloroethane (DDT)

Rossi, Mario; Taddei, Anna Rita; Fasciani, Irene; Maggio, Roberto; Giorgi, Franco

doi:10.1007/s40618-017-0716-9

Cited by 22 publications

(17 citation statements)

References 52 publications

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“…In vitro, a first line of evidence was the antagonistic action of DDT in a TSH-induced cAMP production assay (101), the principal second messenger required for thyroid gland activation. Rossi et al (102,103) investigated this mechanism of action and suggested that DDT could modify the lipid organization of the cell membrane and induce production of extracellular vesicles containing membrane bound TSH receptors (TSHR), thereby inducing failure of the TSH receptor to internalize and prolong TSHR-cAMP signaling. In addition, HCB was shown to reduce viability and inhibit cell cycle progression of FRTL-5 rat thyroid cells along with increased mRNA levels of transforming growth factor-beta (TGF-β1) known to inhibit cell growth in thyroid epithelial cells (104).…”

Section: In Vitro Evidence Of Thyroid Disruptionmentioning

confidence: 99%

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

et al. 2019

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Plant Protection Products, more commonly referred to as pesticides and biocides, are used to control a wide range of yield-reducing pests including insects, fungi, nematodes, and weeds. Concern has been raised that some pesticides may act as endocrine disrupting chemicals (EDCs) with the potential to interfere with the hormone systems of non-target invertebrates and vertebrates, including humans. EDCs act at low doses and particularly vulnerable periods of exposure include pre-and perinatal development. Of critical concern is the number of pesticides with the potential to interfere with the developing nervous system and brain, notably with thyroid hormone signaling. Across vertebrates, thyroid hormone orchestrates metamorphosis, brain development, and metabolism. Pesticide action on thyroid homeostasis can involve interference with TH production and its control, displacement from distributor proteins and liver metabolism. Here we focused on thyroid endpoints for each of the different classes of pesticides reviewing epidemiological and experimental studies carried out both in in vivo and in vitro. We conclude first, that many pesticides were placed on the market with insufficient testing, other than acute or chronic toxicity, and second, that thyroid-specific endpoints for neurodevelopmental effects and mixture assessment are largely absent from regulatory directives.

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Section: In Vitro Evidence Of Thyroid Disruptionmentioning

confidence: 99%

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

et al. 2019

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“…Some pesticides have long been banned in many countries but are still present in the environment, such as DDT, HCB and chlorpyrifos (CPF), and many of these have been examined and investigated for their thyroid-disrupting abilities (Pearce & Braverman 2009). In vitro studies on DDT exposure showed that DDT inhibits TSH release, mainly by affecting cAMP production at the post-receptor step (Santini et al 2003), and DDT can inhibit the activity of TSHR (Rossi et al 2007(Rossi et al , 2009(Rossi et al , 2018. In addition, it has been demonstrated that, in rats, a low dose of DDT increases the concentration of T3 and reduces the level of TSH (Yaglova & Yaglov 2014).…”

Section: Pesticidesmentioning

confidence: 99%

Thyroid function disruptors: from nature to chemicals

Oliveira

Chiamolera

Giannocco

et al. 2019

Journal of Molecular Endocrinology

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The modern concept of thyroid disruptors includes man-made chemicals and bioactive compounds from food that interfere with any aspect of the hypothalamus-pituitary-thyroid axis, thyroid hormone biosynthesis and secretion, blood and transmembrane transport, metabolism and local action of thyroid hormones. This review highlights relevant disruptors that effect populations through their diet: directly from food itself (fish oil and polyunsaturated fatty acids, pepper, coffee, cinnamon and resveratrol/grapes), through vegetable cultivation (pesticides) and from containers for food storage and cooking (bisphenol A, phthalates and polybrominated diphenyl ethers). Due to the vital role of thyroid hormones during every stage of life, we review effects from the gestational period through to adulthood, including evidence from in vitro studies, rodent models, human trials and epidemiological studies.

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“…In experimental studies, rats exposed to DDE exposure exhibit lower free T 4 levels. One target of DDT action on thyroid metabolism may be through the inhibition of TSH-stimulated intracellular accumulation of cyclic adenosine monophosphate (cAMP) by the action of DDT on the TSH receptor ( 184 , 185 , 186 , 187 ). The highly lipophilic DDT may also interfere indirectly with the TSH receptor by altering the phosphor-lipid composition of the thyroid cell membrane, rendering the TSH receptor unable to internalise and instead be released extracellularly in vesicle forms in the presence of DDT ( 188 ).…”

Section: Pesticidesmentioning

confidence: 99%

“…The highly lipophilic DDT may also interfere indirectly with the TSH receptor by altering the phosphor-lipid composition of the thyroid cell membrane, rendering the TSH receptor unable to internalise and instead be released extracellularly in vesicle forms in the presence of DDT ( 188 ). These vesicles have been suggested to initiate autoimmunity favouring the development of Graves’ disease ( 184 ). Mice exposed to DDE also exhibit reduced expression of TTR and Dio2 mRNA, which further explains the reduced free T 4 levels observed ( 189 , 190 ).…”

Section: Pesticidesmentioning

confidence: 99%

Thyroid-disrupting chemicals and brain development: an update

Mughal

Fini

Demeneix

2018

Endocrine Connections

130

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This review covers recent findings on the main categories of thyroid hormone–disrupting chemicals and their effects on brain development. We draw mostly on epidemiological and experimental data published in the last decade. For each chemical class considered, we deal with not only the thyroid hormone–disrupting effects but also briefly mention the main mechanisms by which the same chemicals could modify estrogen and/or androgen signalling, thereby exacerbating adverse effects on endocrine-dependent developmental programmes. Further, we emphasize recent data showing how maternal thyroid hormone signalling during early pregnancy affects not only offspring IQ, but also neurodevelopmental disease risk. These recent findings add to established knowledge on the crucial importance of iodine and thyroid hormone for optimal brain development. We propose that prenatal exposure to mixtures of thyroid hormone–disrupting chemicals provides a plausible biological mechanism contributing to current increases in the incidence of neurodevelopmental disease and IQ loss.

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The cell biology of the thyroid-disrupting mechanism of dichlorodiphenyltrichloroethane (DDT)

Cited by 22 publications

References 52 publications

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

Pesticides With Potential Thyroid Hormone-Disrupting Effects: A Review of Recent Data

Thyroid function disruptors: from nature to chemicals

Thyroid-disrupting chemicals and brain development: an update

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