Endocrine disruptive chemicals: mechanisms of action and involvement in metabolic disorders

Swedenborg, Elin; Rüegg, Joëlle; Mäkelä, Sari; Pongratz, Ingemar

doi:10.1677/jme-08-0132

Cited by 255 publications

(167 citation statements)

References 76 publications

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“…More recently, it has been reported that EDCs are possibly involved in the development of obesity and metabolic syndrome as a number of NRs and AhR are crucially involved in fat metabolism and glucose uptake. 13,72,73) Therefore, exposure to environmental chemicals, including pesticides having NR and AhR activities, not only increases reproductive problems but may also be an exacerbating factor in the development of other debilitating diseases such as metabolic syndrome. Although, to date, 48 members of the NR family have been identified in humans, about half of these are nuclear orphan receptors, the physiological roles and ligands of which are unclear.…”

Section: Resultsmentioning

confidence: 99%

Endocrine-disrupting Potential of Pesticides via Nuclear Receptors and Aryl Hydrocarbon Receptor

Kojima

Takeuchi

Nagai

2010

JOURNAL OF HEALTH SCIENCE

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Nuclear receptors (NRs) and the aryl hydrocarbon receptor (AhR) form a ligand-dependent transcription factor that regulates the genes involved in key physiological functions such as cell growth and differentiation, development, homeostasis, and metabolism. These receptors are potential targets of endocrine-disrupting chemicals (EDCs). To date, many studies have shown that EDCs, such as plasticizers, pesticides, and dioxins, can function as ligands of NRs and AhR. In this review, we focus on recent studies showing that a variety of pesticides, intentionally released into the environment, have agonistic and/or antagonistic activity against NRs and AhR, and present our transactivation assay-based screening results for 200 pesticides against estrogen receptors (ERs), androgen receptor (AR), thyroid hormone receptors (TRs), pregnane X receptor (PXR), peroxisome proliferator-activated receptors (PPARs), and AhR. Our studies have shown that a number of pesticides possess ERα, ERβ, and PXR agonistic activity as well as AR antagonistic activity, whereas none of the pesticides affect the TRα 1 , TRβ 1 , and PPARγ-mediated signaling pathways. In addition, several of the 200 tested pesticides were found to have PPARα and AhR agonistic, and ERα and ERβ antagonistic activity. Although the activities of each of these compounds were weak compared to those of endogenous hormone or dioxins, the endocrine-disrupting potential of pesticides, particularly those which function against ERα/β, AR, and PXR, may reflect that of numerous environmental chemicals.

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Section: Resultsmentioning

confidence: 99%

Endocrine-disrupting Potential of Pesticides via Nuclear Receptors and Aryl Hydrocarbon Receptor

Kojima

Takeuchi

Nagai

2010

JOURNAL OF HEALTH SCIENCE

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“…Hence, in addition to AhR-mediated mechanism, some endocrine disrupting chemical can bind directly to these nuclear receptors either as agonists or as antagonists, thus enhancing or inhibiting the effect of a hormone, respectively. 30,57 Regarding the epidemiological evidence on general populations, a study using the 1999 to 2004 NHANES 28 found a significant 38% increased risk of hypertension among those participants in the highest compared with those in the lowest quartile of serum concentration of total PCBs (odds ratio, 1.38 [95% CI, 1.02-1.87]). Moreover, the congeners identified were not only DL-PCBs (PCB 66 and 118),but also NDLPCBs (PCB 101, 128, and 187).…”

Section: Discussionmentioning

confidence: 99%

Association Between Dietary Intake of Polychlorinated Biphenyls and the Incidence of Hypertension in a Spanish Cohort

et al. 2015

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Polychlorinated biphenyls are persistent organic pollutants that are consumed because of their bioaccumulation through the food chain. Evidence from different sources suggests a positive association between polychlorinated biphenyls exposure and the incidence of hypertension. However, no previous prospective study has investigated this potential relationship in adults. We prospectively assessed the association between dietary intake of polychlorinated biphenyls and the incidence of hypertension in a large cohort. The Seguimiento Universidad de Navarra project is a Spanish cohort of university graduates, most of them health professionals. We included 14521 participants, initially free of hypertension, who were followed-up for a median of 8.3 years. Dietary intake of polychlorinated biphenyls was assessed at baseline through a previously validated 136-item semiquantitative food frequency questionnaire. The published concentration levels of polychlorinated biphenyls measured in samples of food consumed in Spain were used to estimate dietary intake. Multivariable Cox regression models were fitted to estimate hazard ratios and 95% confidence interval for incident hypertension. During follow-up, 1497 incident cases of medically diagnosed hypertension were identified. After adjusting for total energy intake and for potential confounders, participants in the fifth quintile of total polychlorinated biphenyls intake were at higher risk of developing hypertension (adjusted hazard ratio, 1.43 [95% confidence interval, 1.09–1.88; P for trend 0.017]) compared with those in the first quintile. In this Mediterranean cohort, dietary intake of polychlorinated biphenyls, estimated using a food frequency questionnaire, was associated with a higher risk of developing hypertension during follow-up. Nevertheless, further longitudinal studies are needed to confirm our results.

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“…Therefore, they are commonly known or suspected to be endocrine active and may interfere at several control points in the hormone signaling pathways in the body. Therefore, the response cascade of natural hormones can either be inhibited or be excessively enhanced, at the wrong time and in the wrong tissue (Swedenborg et al 2009). Endocrine activity of DDT, its structural cognates and lindane can be due to direct binding with hormone receptors, and their conformational similarity with the receptor-binding portions of natural hormones, mainly of the steroid and diphenylether (thyroxine) structural groups (Gregoraszczuk et al 2008).…”

Section: Toxicity As Endocrine Disruptormentioning

confidence: 99%

Environmental assessment of fate, transport and persistent behavior of dichlorodiphenyltrichloroethanes and hexachlorocyclohexanes in land and water ecosystems

Ahmed

Anawar

Takuwa

et al. 2015

Int. J. Environ. Sci. Technol.

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Many studies have investigated the contamination level, spatial distribution, sources, chiral signals, and potential ecological and public health risks of dichlorodiphenyltrichloroethanes, its metabolites and the isomers of hexachlorocyclohexane in the environment. This study presents a critical review to provide updated knowledge about the fate, persistence, long-range transport and toxicity effects of dichlorodiphenyltrichloroethanes and hexachlorocyclohexanes in the environment on the basis of analytical data between 1990 and 2014. Highest levels were found for dichlorodiphenyltrichloroethanes (200-9300 ng/ L) and hexachlorocyclohexanes (20-36,000 ng/L) with mean values of 1000 and 5600 ng/L, which were 10 and 56 times higher than the European Community allowable residual limit of 100 ng/L, respectively, in Lake Taihu water of China obtained between 1999 and 2000. Levels of dichlorodiphenyltrichloroethanes in sediments and fish species were remarkably higher than hexachlorocyclohexanes. The highest levels of dichlorodiphenyltrichloroethanes in sediments were found up to 780-227,000 ng/g near a production factory in China and 20,000-5,463,000 ng/g in cattle dips disposal areas in Australia. Out of 32 selected locations for common fish species, tilapia had the highest mean concentration of dichlorodiphenyltrichloroethanes up to 3800 ng/g in Noha River of Japan in 2006. Dichlorodiphenyltrichloroethanes and hexachlorocyclohexanes derive from agricultural runoff, industrial and urban wastewater, etc., that ultimately associate with soil and sediments. The carbon-carbon and carbon-chlorine bonds in dichlorodiphenyltrichloroethanes and hexachlorocyclohexanes provide them persistence, lipophilicity and high binding affinity leading to bioaccumulation in the receptor protein. High accumulation of dichlorodiphenyltrichloroethanes and hexachlorocyclohexanes causes mutagenic, carcinogenic and endocrine disrupting toxicity effects to the humans and wildlife.

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Endocrine disruptive chemicals: mechanisms of action and involvement in metabolic disorders

Cited by 255 publications

References 76 publications

Endocrine-disrupting Potential of Pesticides via Nuclear Receptors and Aryl Hydrocarbon Receptor

Endocrine-disrupting Potential of Pesticides via Nuclear Receptors and Aryl Hydrocarbon Receptor

Association Between Dietary Intake of Polychlorinated Biphenyls and the Incidence of Hypertension in a Spanish Cohort

Environmental assessment of fate, transport and persistent behavior of dichlorodiphenyltrichloroethanes and hexachlorocyclohexanes in land and water ecosystems

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