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Persistent organochlorine pollutants with endocrine activity and blood steroid hormone levels in middle-aged men.

ABSTRACT: BACKGROUND: Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. OBJECTIVE: We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. METHODS: We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. RESULTS: DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. CONCLUSIONS: These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease.

SUBMITTER: Emeville E

PROVIDER: S-EPMC3681943 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Persistent organochlorine pollutants with endocrine activity and blood steroid hormone levels in middle-aged men.

Emeville Elise E Giton Frank F Giusti Arnaud A Oliva Alejandro A Fiet Jean J Thomé Jean-Pierre JP Blanchet Pascal P Multigner Luc L

PloS one 20130613 6

<h4>Background</h4>Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results.<h4>Objective</h4>We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosteron ...[more]

PMID: 23785499

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Project description:BackgroundSeveral persistent organochlorine pollutants (POPs) possess endocrine disrupting abilities, thereby potentially leading to an increased risk of obesity and metabolic diseases, especially if the exposure occurs during prenatal life. We have previously found associations between prenatal POP exposures and increased BMI, waist circumference and change in BMI from 5 to 7 years of age, though only among girls with overweight mothers.ObjectivesIn the same birth cohort, we investigated whether prenatal POP exposure was associated with serum concentrations of insulin and leptin among 5-year-old children, thus possibly mediating the association with overweight and obesity at 7 years of age.MethodsThe analyses were based on a prospective Faroese Birth Cohort (n=656), recruited between 1997 and 2000. Major POPs, polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyldichloroethylene (DDE) and hexachlorobenzene (HCB), were measured in maternal pregnancy serum and breast milk. Children were followed-up at the age of 5 years where a non-fasting blood sample was drawn; 520 children (273 boys and 247 girls) had adequate serum amounts available for biomarker analyses by Luminex® technology. Insulin and leptin concentrations were transformed from continuous to binary variables, using the 75th percentile as a cut-off point. Multiple logistic regression was used to investigate associations between prenatal POP exposures and non-fasting serum concentrations of insulin and leptin at age 5 while taking into account confounders.ResultsGirls with highest prenatal POP exposure were more likely to have high non-fasting insulin levels (PCBs 4th quartile: OR=3.71; 95% CI: 1.36, 10.01. DDE 4th quartile: OR=2.75; 95% CI: 1.09, 6.90. HCB 4th quartile: OR=1.98; 95% CI: 1.06, 3.69) compared to girls in the lowest quartile. No significant associations were observed with leptin, or among boys. A mediating effect of insulin or leptin on later obesity was not observed.ConclusionThese findings suggest, that for girls, prenatal exposure to POPs may play a role for later development of metabolic diseases by affecting the level of insulin.

Project description:BackgroundNeoplasms of the mammary gland are among the most common diseases in female domestic dogs (Canis familiaris). It is assumed that reproductive hormones influence tumorigenesis in this species, although the precise role of the endocrine milieu and reproductive state is subject to continuing discussion. In line with this, a recent systematic review of available data on the development of mammary neoplasms revealed weak evidence for risk reduction after neutering and an effect of age at neutering. Investigation of several hormone receptors has revealed decreased expression of estrogen receptor-alpha (ERα, ESR1), progesterone (P4) receptor (PGR), prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) associated with neoplastic differentiation of mammary tissues. In other studies, increased levels of estrogens, progesterone and prolactin were found in serum and/or tissue homogenates of dogs with malignant neoplasms. However, the association between these entities within one animal population was never previously examined. Therefore, this study investigated the association between circulating serum concentrations of estradiol-17β, progesterone and prolactin, and gene expression of ERα (ESR1), ERβ (ESR2), PGR, PRLR, PRL and GHR, with respect to reproductive state (spayed vs. intact) and cycle stage (anestrus vs. diestrus). Additionally, the expression of E-cadherin (CDH-1) was evaluated as a possible indicator of metastatic potential.ResultsFor all receptors, the lowest gene expression was found in malignant tumors compared to normal tissues of affected dogs. Steroid levels were not influenced by their corresponding receptor expression in mammary neoplasms, but increased PRL levels were negatively associated with low PRLR gene expression in malignant tumors. The expression of CDH-1 was influenced by tumor malignancy and cycle stage, i.e., the highest gene expression was found in benign mammary tumors in diestrous dogs compared to normal and malignant mammary tissues of anestrous and spayed dogs.ConclusionsHerein, it has been confirmed that transformation towards malignant neoplasms is associated with significant reduction of gene expression of particular hormone receptors. Only PRLR in malignant tumors seems to be influenced by circulating PRL levels. In dogs, CDH-1 can be used as a prognostic factor; its expression, however, in benign tumors is influenced by cycle stage.

Project description:BACKGROUND:Exposure to persistent organic pollutants (POPs) may predispose to the development of type 2 diabetes (T2D), but prospective human evidence is scarce. OBJECTIVES:We investigated the association between plasma-POP concentrations in the late 1990s and incident T2D over 11 years of follow-up in the Nurses' Health Study II. DISCUSSION:Three organochlorine pesticides and 20 polychlorinated biphenyls (PCBs) were measured in banked plasma from 793 case-control pairs of T2D. In a multiviarate-adjusted model, T2D ORs (95%CIs) comparing extreme POP tertiles (high vs. low) were 1.67 (1.24, 2.23; Ptrend < 0.001) for hexachlorobenzene (HCB), 3.62 (2.57, 5.11; Ptrend < 0.001) for β-hexachlorocyclohexane (β-HCH), 1.55 (1.13, 2.13; Ptrend = 0.05) for p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and 1.95 (1.42, 2.69; Ptrend < 0.001) for total dioxin-like PCBs (DL-PCBs) which included 5 mono-ortho congeners, PCB-105, 118, 156, 157, and 167. Adjustment for previous weight change and body mass index (BMI) at blood draw attenuated these associations, but that for DL-PCBs remained (OR[95% CI] = 1.78[1.14, 2.76]; Ptrend = 0.006). Age, breastfeeding history, previous weight change and BMI at blood draw were significant predictors of plasma POP concentrations. In addition, we found significant interactions of POPs and weight change before blood draw on T2D risk. ORs (95%CIs) of T2D comparing extreme (high vs. low) POP groups were 2.00 (1.02, 3.92; Ptrend = 0.01) for HCB, 2.69 (1.34, 5.40; Ptrend < 0.001) for β-HCH, and 2.41 (1.22, 4.77; Ptrend < 0.001) for DL-PCBs in the lowest weight gain group, whereas these values were 1.29 (0.73, 2.28; Ptrend = 0.46; Pinteraction = 0.04) for HCB, 1.41 (0.77, 2.60; Ptrend = 0.24; Pinteraction = 0.003) for β-HCH, and 0.90 (0.50, 1.63; Ptrend = 0.61; Pinteraction = 0.01) for DL-PCBs in the highest weight-gain group. CONCLUSIONS:Our findings suggest that elevated POP exposure may have diabetogenic potential. These data also highlight the impact of lifestyle factors, especially history of weight gain, on circulating POP concentrations and their associations with subsequent T2D risk.

Project description:Persistent organic pollutants (POPs) have been banned over the last decades for being damaged to the environment and to the health of humans and animals. However, due to their lipophilic nature and resistance to degradation, they are frequently detected in biological samples. Its presence has been associated with the increased risk of suffering from different diseases in human series, being newborns and children especially sensitive. The present data reports umbilical cord blood levels of twenty organochlorine pesticides (aldrin, dieldrin, endrin, o,p'-DDD, p,p'-DDD, o,p'-DDE, p,p'-DDE, o,p'-DDT, p,p'-DDT, endosulfan alfa, endosulfan beta, endosulfan sulphate, heptachlor, HCB, αHCH, βHCH, δHCH, lindane, methoxychlor and mirex), eighteen polychlorinated biphenyls (congeners 28, 52, 77, 81, 101, 105, 114, 118, 123, 126, 138, 153, 156, 157, 167, 169, 180 and 189), eight bromodiphenyl ethers (congeners 28, 47, 85, 99, 100, 153, 154 and 183), and sixteen polycyclic aromatic hydrocarbons (acenaphthalene, acenaphthene, anthracene, benzo(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, benzo(g,h,i)perylene, benzo(k)fluoranthene, chrysene, dibenzo(a,h)anthracene, fluoranthene, fluorine, indene(1,2,3-cd)pyrene, naphthalene, phenanthrene and pyrene). A total of 447 samples, representing 86.6% of the total births during the recruited period (March 1, 2015, to April 30, 2016), were available for POP analyses. POPs were determined in a Gas Chromatography (GC) system equipped with an automated sampler (Models 7890B and 7693; Agilent Technologies, Palo Alto, CA, USA) for gas chromatographic separations. The detection of the analytes was performed using a Triple Quad 7010 mass spectrometer (Agilent Technologies). All of the measurements were performed as triplicate measurements, and the means were used for the calculations. Data are reported in ng/mL. The present data also includes birth parameters, including weight, length, cranial perimeter, Apgar score and congenital malformations, and data referred to mothers (harmful habits, chronic diseases, and anthropometric/demographic characteristics).

Project description:Essentials Endogenous hormone levels' influence on hemostatic factor levels is not fully characterized. We tested for associations of endogenous hormone with hemostatic factor levels in postmenopause. Estrone levels were inversely associated with the natural anticoagulant, protein S antigen. Dehydroepiandrosterone sulfate levels were inversely associated with thrombin generation.SummaryBackground Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 μg mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.

Dataset Information

Persistent organochlorine pollutants with endocrine activity and blood steroid hormone levels in middle-aged men.

Publications

Persistent organochlorine pollutants with endocrine activity and blood steroid hormone levels in middle-aged men.

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