A chemical screening system for glucocorticoid stress hormone signaling in an intact vertebrate

完整脊椎动物中糖皮质激素应激激素信号的化学筛选系统

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作者:Benjamin D Weger, Meltem Weger, Michael Nusser, Gerald Brenner-Weiss, Thomas Dickmeis

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.

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