title: Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat.
abstract: Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and testis (intact) proteomes in rats after 3 days of exposure. The adrenal accounted for most of the serum progesterone and all of the corticosterone increases in intact and castrated males. Serum luteinizing hormone, androstenedione, and testosterone in intact males shared a non-monotonic response suggesting transition from an acute stimulatory to a latent inhibitory response to exposure. Eight adrenal proteins were significantly altered with dose. There were unique proteomic changes between the adrenals of intact and castrated males. Six testis proteins in intact males had non-monotonic responses that significantly correlated with serum testosterone. Different dose-response curves for steroids and proteins in the adrenal and testis reveal novel adverse outcome pathways in intact and castrated male rats.
authors.affiliation: Oak Ridge Institute for Science and Education (ORISE), Research Participation Program, Oak Ridge, TN 37831, United States.
authors.forename: Brandy W
authors.initials: BW
authors.lastname: Riffle
authors.affiliation: Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency (U.S. EPA), Research Triangle Park (RTP), NC 27711, United States.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Klinefelter
authors.affiliation: Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency (U.S. EPA), Research Triangle Park (RTP), NC 27711, United States.
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Cooper
authors.affiliation: Proteomic Research Core, NHEERL, ORD, U.S. EPA, Research Triangle Park (RTP), NC 27711, United States.
authors.forename: Witold M
authors.initials: WM
authors.lastname: Winnik
authors.affiliation: Proteomic Research Core, NHEERL, ORD, U.S. EPA, Research Triangle Park (RTP), NC 27711, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Swank
authors.affiliation: Atlantic Ecology Division, NHEERL, ORD, U.S. EPA, Narragansett, RI 02882, United States.
authors.forename: Saro
authors.initials: S
authors.lastname: Jayaraman
authors.affiliation: Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency (U.S. EPA), Research Triangle Park (RTP), NC 27711, United States.
authors.forename: Juan
authors.initials: J
authors.lastname: Suarez
authors.affiliation: Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency (U.S. EPA), Research Triangle Park (RTP), NC 27711, United States.
authors.forename: Deborah
authors.initials: D
authors.lastname: Best
authors.affiliation: Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency (U.S. EPA), Research Triangle Park (RTP), NC 27711, United States. Electronic address: laws.susan@epa.gov.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Laws
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000735:Androstenedione / Q000097:blood; D000818:Animals; D001280:Atrazine / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D002369:Castration; D003345:Corticosterone / Q000097:blood; D006540:Herbicides / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011374:Progesterone / Q000097:blood; D020543:Proteome; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D006540:Herbicides; D020543:Proteome; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D007986:Luteinizing Hormone; D001280:Atrazine; D003345:Corticosterone
keywords: Atrazine; Corticosterone; Hypothalamic-pituitary-adrenal (HPA) axis; Proteomics; Steroidogenesis