title: A chemical screening system for glucocorticoid stress hormone signaling in an intact vertebrate.
abstract: Glucocorticoids, steroid hormones of the adrenal gland, are an integral part of the stress response and regulate glucose metabolism. Natural and synthetic glucocorticoids are widely used in anti-inflammatory therapy but can have severe side effects. In vivo tests are needed to identify novel glucocorticoids and to screen compounds for unwanted effects on glucocorticoid signaling. We created the Glucocorticoid Responsive In vivo Zebrafish Luciferase activitY assay to monitor glucocorticoid signaling in vivo. The GRIZLY assay detects stress-induced glucocorticoid production in single zebrafish larvae, measures disruption of glucocorticoid signaling by an organotin pollutant metabolite, and specifically identifies a compound stimulating endogenous glucocorticoid production in a chemical screen. Our assay has broad applications in stress research, environmental monitoring, and drug discovery.
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Weger
authors.forename: Meltem
authors.initials: M
authors.lastname: Weger
authors.forename: Michael
authors.initials: M
authors.lastname: Nusser
authors.forename: Gerald
authors.initials: G
authors.lastname: Brenner-Weiss
authors.forename: Thomas
authors.initials: T
authors.lastname: Dickmeis
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009947:Organotin Compounds / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D015027:Zebrafish
chemical_list: D005938:Glucocorticoids; D009947:Organotin Compounds