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Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat
Riffle, B., G. Klinefelter, R. Cooper, W. Winnik, A. Swank, Saro Jayaraman, J. Suarez, D. Best, AND S. Laws. Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 47:59-69, (2014).
This manuscript describes novel molecular events associated with altered steroidogenesis following exposure to an environmental chemical. Results demonstrate the impact of adrenal steroids on the regulation of the hypothalamic-pituitary-gonadal axis and production of gonadal steroids. Data from this study will be used for the development of an adverse outcome pathway.
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.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION
ENDOCRINE TOXICOLOGY BRANCH