title: Direct and indirect impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on adult mouse Leydig cells: an in vitro study.
abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related substances are ubiquitous environmental pollutants that exert adverse effects on reproductive processes. In testis, Leydig cells which produce testosterone are under hormonal and local control exerted by cytokines including TNFα. Using mouse Leydig primary cell cultures as a model, we studied the effects of TCDD on the steroidogenic outcome of Leydig cells and the gene expression levels of Ccl5 and Cxcl4, previously shown to be target genes of TCDD in testis. We found that TCDD did not alter the steroidogenic outcome of Leydig cells but that it up-regulated Cxcl4 gene expression levels. TCDD also impacted Ccl5 gene expression when cells had been co-treated with TNFα. TCDD action probably initiated with binding to the aryl hydrocarbon receptor (AhR) present on Leydig cells. TCDD regulated the gene expression levels of AhR (transient down-regulation) and its repressor AhRR and Cyp1b1 (up-regulation). The trophic human chorionic gonadotropin (hCG) hormone did not impact AhR, its repressor AhRR or Cyp1b1 but it opposed the TCDD-enhanced AhRR mRNA levels. Conversely, TNFα stimulated AhR gene expression levels. Collectively, it is suggested that the impact of TCDD on expression of target genes in Leydig cells may operate under the complex network of hormones and cytokines.
authors: INSERM, U1060, CarMeN, Laboratoire Lyonnais de Recherche en Cardiovasculaire, Métabolisme, Diabétologie et Nutrition, F-69921 Oullins, France.
authors: Danielle
authors: D
authors: Naville
authors: Diane
authors: D
authors: Rebourcet
authors: Marie-Agnès
authors: MA
authors: Chauvin
authors: Nathalie
authors: N
authors: Vega
authors: Audrey
authors: A
authors: Jalabert
authors: Michèle
authors: M
authors: Vigier
authors: Emmanuelle
authors: E
authors: Loizon
authors: Martine
authors: M
authors: Bégeot
authors: Brigitte
authors: B
authors: Le Magueresse-Battistoni
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000187:drug effects; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010978:Platelet Factor 4 / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis / Q000187:drug effects; D012097:Repressor Proteins / Q000096:biosynthesis / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D051792:Basic Helix-Loop-Helix Proteins; D018946:Chemokine CCL5; D065633:Cytochrome P-450 CYP1B1; D010978:Platelet Factor 4; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; D013739:Testosterone; D014409:Tumor Necrosis Factor-alpha; C117300:Ahrr protein, mouse; C585496:CYP1B1 protein, human; C585498:Cyp1b1 protein, mouse