Triazine Herbicides and Their Chlorometabolites Alter Steroidogenesis in BLTK1 Murine Leydig Cells

• DOI: 10.1093/toxsci/kft096
• Publication Date: 2013-04-17T04:13:01Z
• Authors: Agnes L. Forgacs; Michelle L. D’Souza; Ilpo T. Huhtaniemi; Nafis A. Rahman; Timothy R. Zachar...
• Keywords: Human chorionic gonadotropin; CYP17A1; Simazine

The triazine herbicides, atrazine (ATR), simazine (SIM), propazine (PRO), terbuthylazine (TBA), and their chlorinated metabolites have been implicated in the etiology of testicular dysgenesis by altering steroidogenesis. To further investigate effects on testosterone biosynthesis, BLTK1 cells were used to evaluate steroid hormone levels genome-wide gene expression. are a novel murine Leydig cell line possessing an intact steroidogenic pathway with constitutive low basal (T) that can be induced recombinant human chorionic gonadotropin (rhCG). Triazines (ATR, SIM, PRO, TBA) chlorometabolites (DEA, DIA, DACT) concentration-dependent (1, 3, 10, 30, 100, 300, 600 µM) increases progesterone (P) T relative solvent control at 24h. Temporal analysis (300 µM 1, 2, 4, 8, 12, 24, or 48h) elicited comparable P profiles all compounds varying efficacies (ATR > TBA PRO DEA DIA DACT >> SIM) similar rhCG. ATR time- induction Star, Hsd3b6, Hsd17b3 mRNA levels, whereas Hsd3b1, Cyp17a1, Srd5a1 expression was repressed. albeit weaker effects, SIM had negligible consistent levels. Whole-genome microarrays identified 797 differentially regulated genes 300 ATR, occurring primarily later time points (> 12h) overrepresented functions associated steroidogenesis cholesterol metabolism. These results indicate changes partially attributed triazine-elicited alterations