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Janice E. Chambers - One of the best experts on this subject based on the ideXlab platform.

  • Association of serum levels of p,p'- Dichlorodiphenyldichloroethylene (DDE) with type 2 diabetes in African American and Caucasian adult men from agricultural (Delta) and non-agricultural (non-Delta) regions of Mississippi.
    Journal of toxicology and environmental health. Part A, 2019
    Co-Authors: Edward C. Meek, Dana Dale Jones, J. Allen Crow, Robert W. Wills, William H. Cooke, Janice E. Chambers
    Abstract:

    Epidemiological associations were reported in several studies between persistent organochlorine organic pollutants and type 2 diabetes mellitus (T2D). Mississippi is a highly agricultural state in the USA, particularly the Delta region, with previous high usage of organochlorine (OC) insecticides such as p,p'- dichlorodiphenyltrichloroethane (DDT). In addition, there is a high proportion of African Americans who display elevated prevalence of T2D. Therefore, this State provides an important dataset for further investigating any relationship between OC compounds and metabolic diseases. The aim of this study was to assess whether soil and serum levels of OC compounds, such as p,p'- Dichlorodiphenyldichloroethylene (DDE), arising from the heavy historical use of legacy OC insecticides, might serve as an environmental public health indicator for T2D occurrence. Soil samples from 60 Delta and 60 non-Delta sites randomly selected were analyzed for the presence of OC compounds. A retrospective cohort study of adult men (150 from each region) was recruited to provide a blood sample for OC compound quantitation and select demographic and clinical information including T2D. Using multivariable logistic regression, an association was found between increasing serum DDE levels and T2D occurrence in non-Delta participants (those subjects with lower serum DDE levels), as opposed to Delta participants (individuals with higher serum DDE levels). Thus, while there was a relationship between serum DDE levels and T2D in those with lower burdens of DDE, the lack of association in those with higher levels of DDE indicates a complex non-monotonic correlation between serum DDE levels and T2D occurrence complicating the goal of finding a public health marker for T2D. Abbreviations: BMI, body mass index; CVD, cardiovascular disease; CDC, Center for Disease Control, United States of America; DDE, p,p'- Dichlorodiphenyldichloroethylene; DDT, p,p'- dichlorodiphenyltrichloroethane; GC/MS, gas chromatography/mass spectrometry; GIS, geographic information system; GPS, global positioning system; HDL, high-density lipoprotein; HTN, hypertension; IDW, inverse distance weighting; IRB, Institutional Review Board; LDL, low-density lipoprotein; LOQ, limit of quantitation; NHANES, National Health and Nutrition Examination Surveys; POPs, persistent organic pollutants; OC, organochlorine; PCB, polychlorinated biphenyl; SIM, single-ion monitoring; T2D, type 2 diabetes mellitus; USA, United States of America.

  • Association of serum levels of p,p’- Dichlorodiphenyldichloroethylene (DDE) with type 2 diabetes in African American and Caucasian adult men from agricultural (Delta) and non-agricultural (non-Delta) regions of Mississippi
    2019
    Co-Authors: Edward C. Meek, Dana Dale Jones, Robert W. Wills, William H. Cooke, Allen J. Crow, Janice E. Chambers
    Abstract:

    Epidemiological associations were reported in several studies between persistent organochlorine organic pollutants and type 2 diabetes mellitus (T2D). Mississippi is a highly agricultural state in the USA, particularly the Delta region, with previous high usage of organochlorine (OC) insecticides such as p,p’- dichlorodiphenyltrichloroethane (DDT). In addition, there is a high proportion of African Americans who display elevated prevalence of T2D. Therefore, this State provides an important dataset for further investigating any relationship between OC compounds and metabolic diseases. The aim of this study was to assess whether soil and serum levels of OC compounds, such as p,p’- Dichlorodiphenyldichloroethylene (DDE), arising from the heavy historical use of legacy OC insecticides, might serve as an environmental public health indicator for T2D occurrence. Soil samples from 60 Delta and 60 non-Delta sites randomly selected were analyzed for the presence of OC compounds. A retrospective cohort study of adult men (150 from each region) was recruited to provide a blood sample for OC compound quantitation and select demographic and clinical information including T2D. Using multivariable logistic regression, an association was found between increasing serum DDE levels and T2D occurrence in non-Delta participants (those subjects with lower serum DDE levels), as opposed to Delta participants (individuals with higher serum DDE levels). Thus, while there was a relationship between serum DDE levels and T2D in those with lower burdens of DDE, the lack of association in those with higher levels of DDE indicates a complex non-monotonic correlation between serum DDE levels and T2D occurrence complicating the goal of finding a public health marker for T2D. Abbreviations: BMI, body mass index; CVD, cardiovascular disease; CDC, Center for Disease Control, United States of America; DDE, p,p’- Dichlorodiphenyldichloroethylene; DDT, p,p’- dichlorodiphenyltrichloroethane; GC/MS, gas chromatography/mass spectrometry; GIS, geographic information system; GPS, global positioning system; HDL, high-density lipoprotein; HTN, hypertension; IDW, inverse distance weighting; IRB, Institutional Review Board; LDL, low-density lipoprotein; LOQ, limit of quantitation; NHANES, National Health and Nutrition Examination Surveys; POPs, persistent organic pollutants; OC, organochlorine; PCB, polychlorinated biphenyl; SIM, single-ion monitoring; T2D, type 2 diabetes mellitus; USA, United States of America.

  • exposure to p p Dichlorodiphenyldichloroethylene dde induces fasting hyperglycemia without insulin resistance in male c57bl 6h mice
    Toxicology, 2014
    Co-Authors: George E Howell, Edward C. Meek, Jessica Kilic, Mariel Mohns, Charlee Mulligan, Janice E. Chambers
    Abstract:

    Abstract Approximately 8.3% of the United States (U.S.) population have either diagnosed or undiagnosed diabetes mellitus. Out of all the cases of diabetes mellitus, approximately 90–95% of these cases are type 2 diabetes mellitus (T2D). Although the exact cause of T2D remains elusive, predisposing factors include age, weight, poor diet, and a sedentary lifestyle. Until recently the association between exposure to environmental contaminants and the occurrence of diabetes had been unexplored. However, recent epidemiological studies have revealed that elevated serum concentrations of certain persistent organic pollutants (POPs), especially organochlorine pesticides, are positively associated with increased prevalence of T2D and insulin resistance. The current study seeks to investigate if this association is causative or coincidental. Male C57BL/6H mice were exposed to DDE (2.0 mg/kg or 0.4 mg/kg) or vehicle (corn oil; 1 mL/kg) for 5 days via oral gavage; fasting blood glucose, glucose tolerance, and insulin challenge tests were performed following a 7 day resting period. Exposure to DDE caused significant hyperglycemia compared to vehicle and this hyperglycemic effect persisted for up to 21 days following cessation of DDE administration. Intraperitoneal glucose tolerance tests and phosphorylation of Akt in the liver, skeletal muscle, and adipose tissue following insulin challenge were comparable between vehicle and DDE treated animals. To determine the direct effect of exposure to DDE on glucose uptake, in vitro glucose uptake assays following DDE exposure were performed in L6 myotubules and 3T3-L1 adipocytes. In summary, subacute exposure to DDE does produce fasting hyperglycemia, but this fasting hyperglycemia does not appear to be mediated by insulin resistance. Thus, the current study reveals that subacute exposure to DDE does alter systemic glucose homeostasis and may be a contributing factor to the development of hyperglycemia associated with diabetes.

Brenda Eskenazi - One of the best experts on this subject based on the ideXlab platform.

  • Predicting Prenatal Exposure to Polybrominated Diphenyl Ethers (Pbdes), p,p-Dichlorodiphenyltrichloroethane (p,p-DDT), and p,p-Dichlorodiphenyldichloroethylene (p,p-DDE) from Maternal and Child Blood Levels 9 Years after Delivery
    ISEE Conference Abstracts, 2014
    Co-Authors: Fraser W. Gaspar, Jonathan Chevrier, Marc-andré Verner, Robert B. Gunier, Andreas Sjödin, Asa Bradman, Brenda Eskenazi
    Abstract:

    Prenatal exposure to polybrominated diphenyl ethers (PBDEs), p,p’-dichlorodiphenyltrichloroethane (p,p’-DDT), and p,p’-Dichlorodiphenyldichloroethylene (p,p’-DDE) have been associated with adverse ...

  • in utero exposure to dichlorodiphenyltrichloroethane ddt and Dichlorodiphenyldichloroethylene dde and neurodevelopment among young mexican american children
    Pediatrics, 2006
    Co-Authors: Brenda Eskenazi, Asa Bradman, Amy R. Marks, Laura Fenster, Caroline Johnson, Dana B Barr, Nicholas P. Jewell
    Abstract:

    Objective We investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexican farm-workers' children in California. Methods Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p'-DDT, o,p'-DDT, and p,p'-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months. Results We found a approximately 2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p'-DDT levels at 6 and 12 months (but not 24 months) and p,p'-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p'-DDT and o,p'-DDT at 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure, breastfeeding was usually associated positively with Bayley scale scores. Conclusions Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weigh its benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment.

  • in utero exposure to dichlorodiphenyltrichloroethane ddt and Dichlorodiphenyldichloroethylene dde and neurodevelopment among young mexican american children
    Pediatrics, 2006
    Co-Authors: Brenda Eskenazi, Asa Bradman, Amy R. Marks, Laura Fenster, Caroline Johnson, Dana B Barr, Nicholas P. Jewell
    Abstract:

    OBJECTIVE. We investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexican farm-workers9 children in California. METHODS. Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p′-DDT, o,p′-DDT, and p,p′-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months. RESULTS. We found a ∼2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p′-DDT levels at 6 and 12 months (but not 24 months) and p,p′-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p′-DDT and o,p′-DDT at 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure, breastfeeding was usually associated positively with Bayley scale scores. CONCLUSIONS. Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weigh its benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment.

  • In Utero Exposure to Dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and Neurodevelopment Among Young Mexican
    2006
    Co-Authors: Brenda Eskenazi, Asa Bradman, Amy R. Marks, Laura Fenster, Caroline Johnson, Nicholas P. Jewell
    Abstract:

    OBJECTIVE. We investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexican farm-workers’ children in California. METHODS. Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p-DDT, o,p-DDT, and p,p-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months. RESULTS. We found a 2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p-DDT levels at 6 and 12 months (but not 24 months) and p,p-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p-DDT and o,p-DDT at 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure, breastfeeding was usually associated positively with Bayley scale scores. CONCLUSIONS. Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weigh its benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment.

Nicholas P. Jewell - One of the best experts on this subject based on the ideXlab platform.

  • in utero exposure to dichlorodiphenyltrichloroethane ddt and Dichlorodiphenyldichloroethylene dde and neurodevelopment among young mexican american children
    Pediatrics, 2006
    Co-Authors: Brenda Eskenazi, Asa Bradman, Amy R. Marks, Laura Fenster, Caroline Johnson, Dana B Barr, Nicholas P. Jewell
    Abstract:

    OBJECTIVE. We investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexican farm-workers9 children in California. METHODS. Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p′-DDT, o,p′-DDT, and p,p′-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months. RESULTS. We found a ∼2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p′-DDT levels at 6 and 12 months (but not 24 months) and p,p′-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p′-DDT and o,p′-DDT at 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure, breastfeeding was usually associated positively with Bayley scale scores. CONCLUSIONS. Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weigh its benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment.

  • in utero exposure to dichlorodiphenyltrichloroethane ddt and Dichlorodiphenyldichloroethylene dde and neurodevelopment among young mexican american children
    Pediatrics, 2006
    Co-Authors: Brenda Eskenazi, Asa Bradman, Amy R. Marks, Laura Fenster, Caroline Johnson, Dana B Barr, Nicholas P. Jewell
    Abstract:

    Objective We investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexican farm-workers' children in California. Methods Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p'-DDT, o,p'-DDT, and p,p'-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months. Results We found a approximately 2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p'-DDT levels at 6 and 12 months (but not 24 months) and p,p'-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p'-DDT and o,p'-DDT at 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure, breastfeeding was usually associated positively with Bayley scale scores. Conclusions Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weigh its benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment.

  • In Utero Exposure to Dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and Neurodevelopment Among Young Mexican
    2006
    Co-Authors: Brenda Eskenazi, Asa Bradman, Amy R. Marks, Laura Fenster, Caroline Johnson, Nicholas P. Jewell
    Abstract:

    OBJECTIVE. We investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexican farm-workers’ children in California. METHODS. Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p-DDT, o,p-DDT, and p,p-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months. RESULTS. We found a 2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p-DDT levels at 6 and 12 months (but not 24 months) and p,p-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p-DDT and o,p-DDT at 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure, breastfeeding was usually associated positively with Bayley scale scores. CONCLUSIONS. Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weigh its benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment.

Yeonhwa Park - One of the best experts on this subject based on the ideXlab platform.

  • 4,4'-Dichlorodiphenyltrichloroethane (DDT) and 4,4'-Dichlorodiphenyldichloroethylene (DDE) inhibit myogenesis in C2C12 myoblasts.
    Journal of the science of food and agriculture, 2017
    Co-Authors: Jonggun Kim, Min Young Park, Yoo Kim, Kyong Sup Yoon, John M. Clark, Yeonhwa Park, Kwang Youn Whang
    Abstract:

    Most countries have banned the use of 4,4'-dichlorodiphenyltrichloroethane (DDT). However, owing to its extremely high lipophilic characteristics, DDT and its metabolite 4,4'-Dichlorodiphenyldichloroethylene (DDE) are ubiquitous in the environment and in many types of food. The positive correlation between exposure to insecticides, including DDT and DDE, and weight gain, resulting in impaired energy metabolism in offspring following perinatal DDT and DDE exposure, was previously reported. Therefore the influence of DDT and DDE on myogenesis using C2C12 myoblasts was investigated in this study.; Results: DDT and DDE decreased myotube formation dose- and time-dependently. Among myogenic regulatory factors, DDT and DDE mainly decreased MyoD1 and Myf5 expression. DDT and DDE treatment also altered Myostatin expression, phosphorylation of protein kinase B, p70 ribosomal protein S6 kinase, forkhead box O protein 3 and mammalian target of rapamycin, resulting in attenuation of myotube formation.; Conclusion: These results may have significant implications for understanding the effects of developmental exposure of DDT and DDE on myogenesis and development of obesity and type 2 diabetes later in life. © 2017 Society of Chemical Industry.; © 2017 Society of Chemical Industry.

  • 4 4 dichlorodiphenyltrichloroethane ddt and 4 4 Dichlorodiphenyldichloroethylene dde promote adipogenesis in 3t3 l1 adipocyte cell culture
    Pesticide Biochemistry and Physiology, 2016
    Co-Authors: Jonggun Kim, Kyong Sup Yoon, Kwang Youn Whang, Quancai Sun, Yiren Yue, Marshall J Clark, Yeonhwa Park
    Abstract:

    4,4'-Dichlorodiphenyltrichloroethane (DDT), a chlorinated hydrocarbon insecticide, was extensively used in the 1940s and 1950s. DDT is mainly metabolically converted into 4,4'-Dichlorodiphenyldichloroethylene (DDE). Even though most countries banned DDT in the 1970s, due to the highly lipophilic nature and very stable characteristics, DDT and its metabolites are present ubiquitously in the environment, including food. Recently, there are publications on relationships between exposure to insecticides, including DDT and DDE, and weight gain and altered glucose homeostasis. However, there are limited reports regarding DDT or DDE and adipogenesis, thus we investigated effects of DDT and DDE on adipogenesis using 3T3-L1 adipocytes. Treatment of DDT or DDE resulted in increased lipid accumulation accompanied by increased expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome-proliferator activated receptor-γ (PPARγ), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), adipose triglyceride lipase, and leptin. Moreover, treatment of DDT or DDE increased protein levels of C/EBPα, PPARγ, AMP-activated protein kinase-α (AMPKα), and ACC, while significant decrease of phosphorylated forms of AMPKα and ACC were observed. These finding suggest that increased lipid accumulation caused by DDT and DDE may mediate AMPKα pathway in 3T3-L1 adipocytes.

P.j. Chedrese - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of basal and stimulated progesterone synthesis by Dichlorodiphenyldichloroethylene and methoxychlor in a stable pig granulosa cell line.
    Reproduction, 2001
    Co-Authors: N.k. Crellin, Hg Kang, Cl Swan, P.j. Chedrese
    Abstract:

    The effects of the insecticide Dichlorodiphenyldichloroethylene (DDE) and methoxychlor in a stable pig granulosa cell line, JC-410, were investigated. The studies of DDE and methoxychlor were conducted in combination with studies of cholera toxin, the protein kinase A activator that stimulates cAMP and progesterone synthesis and gene expression of P450 cholesterol side chain cleavage (P450scc), which converts cholesterol to pregnenolone. Administration of DDE at 3000 and 10 000 ng ml ‐1 was found to decrease progesterone synthesis 0.49- and 0.25fold, respectively, and to block the stimulatory effect of 100 ng cholera toxin ml ‐1 , after 24 h incubation. At 1‐100 ng ml ‐1 , methoxychlor did not affect progesterone synthesis after 48 h incubation. However, 1000 ng methoxychlor ml ‐1 decreased progesterone synthesis 0.32-fold, and both 100 and 1000 ng methoxychlor ml ‐1 blocked the stimulatory effect of cholera toxin. At 3000 and 10 000 ng ml ‐1 , DDE decreased cAMP synthesis 0.66and 0.36-fold, respectively. At 300, 3000 and 10 000 ng ml ‐1 , DDE also decreased cholera toxin-stimulated cAMP synthesis 0.84-, 0.68-, and 0.52-fold, respectively. Administration of 1‐100 ng methoxychlor ml ‐1 did not affect basal or cholera toxin-stimulated cAMP synthesis. Cholera toxin increased P450scc mRNA 1.4-fold after 24 h incubation, while 3000 and 10 000 ng DDE ml ‐1 led to 0.39- and 0.18-fold reductions, respectively. The stimulatory effect of cholera toxin on P450scc mRNA was blocked by 3000 and 10 000 ng DDE ml ‐1 . Cholera toxin increased P450scc mRNA 3.48-fold after 48 h incubation, while 100 and 1000 ng methoxychlor ml ‐1 increased P450scc mRNA 1.79- and 3.0-fold, respectively, and further increased the stimulatory effect of cholera toxin 6.47- and 5.44-fold, respectively. The results of the present study indicate that DDE inhibits granulosa cell steroidogenesis by affecting cAMP production and P450scc gene expression. However, methoxychlor appears to inhibit steroidogenesis by a mechanism occurring before the conversion of cholesterol into pregnenolone.

  • Dichlorodiphenyldichloroethylene potentiates the effect of protein kinase A pathway activators on progesterone synthesis in cultured porcine granulosa cells.
    Biology of reproduction, 1999
    Co-Authors: N.k. Crellin, M.r. Rodway, Cynthia L. Swan, C. Gillio-meina, P.j. Chedrese
    Abstract:

    The insecticide dichlorodiphenyltrichloroethane (DDT) and its major metabolite p,p'-Dichlorodiphenyldichloroethylene (DDE) have been implicated as endocrine-modulating chemicals. The DDT metabolite p, p'-DDE has been found contaminating human tissues and follicular fluid because of dietary exposure. We investigated the effects of DDE on progesterone synthesis in a stable porcine granulosa cell line, JC-410, and in primary cultures of porcine granulosa cells. Progesterone synthesis was not affected by 0.1-100 ng/ml DDE in the JC-410 cells. However, 10 ng/ml DDE increased 8-bromo-cAMP (8-Br-cAMP)-stimulated progesterone synthesis 0.4-fold (P < 0.05) over the levels observed with 1 mM 8-Br-cAMP alone. The effect of cholera toxin (CT) on progesterone synthesis was increased 0.7-fold (P < 0.05) by 10 ng/ml DDE over the value observed with 30 ng/ml CT alone. In primary cultures of porcine granulosa cells, 10 ng/ml DDE potentiated CT-stimulated progesterone synthesis 1.2-fold over the value observed with CT alone. In the JC-410 cells, 1 and 10 ng/ml DDE increased CT-stimulated cytochrome P450-cholesterol side-chain cleavage (P450(scc)) mRNA levels 0.3- and 0.4-fold, respectively, over the values obtained with CT alone. Neither basal nor CT-stimulated cAMP levels were changed by DDE. We conclude that DDE affects granulosa cell response to protein kinase A activators by altering the expression of the P450(scc) gene.