title: Dichlorodiphenyldichloroethylene potentiates the effect of protein kinase A pathway activators on progesterone synthesis in cultured porcine granulosa cells.
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.
authors.affiliation: Reproductive Biology Research Unit, Department of Obstetrics and Gynecology and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N OW8.
authors.forename: N K
authors.initials: NK
authors.lastname: Crellin
authors.forename: M R
authors.initials: MR
authors.lastname: Rodway
authors.forename: C L
authors.initials: CL
authors.lastname: Swan
authors.forename: C
authors.initials: C
authors.lastname: Gillio-Meina
authors.forename: P J
authors.initials: PJ
authors.lastname: Chedrese
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003633:Dichlorodiphenyl Dichloroethylene / Q000494:pharmacology*; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis*; D013552:Swine
chemical_list: D007306:Insecticides; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone; D003633:Dichlorodiphenyl Dichloroethylene; D002772:Cholera Toxin; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017868:Cyclic AMP-Dependent Protein Kinases