Transcriptional and metabolic effects of glucocorticoid receptor α and β signaling in zebrafish.

摘要: In humans and zebrafish, 2 glucocorticoid (GC) receptor (GR) splice variants exist: the canonical GR α-isoform (GRα), GRβ. present study, we have used zebrafish model system in order to reveal genes affected by each of these isoforms. By injecting embryos with different splice-blocking morpholinos, could knock down both isoforms or target alternative splicing pre-mRNA favor addition, specific GRβ overexpression was achieved mRNA. Embryos were treated synthetic GC dexamethasone, transcriptome analysis performed. Two distinct gene clusters found that regulated GRα: one GRα under basal conditions (presence endogenous cortisol only), upon increased activation (using a pharmacological dose dexamathasone). may act as dominant-negative inhibitor when is overexpressed expression level knocked simultaneously. However, without knockdown, no evidence for this activity found. data indicate regulation transcription through other mechanisms action We also investigated concentrations several metabolites using nuclear magnetic resonance spectroscopy. dexamethasone treatment knockdown together had opposite effects on glucose, amino acid, fatty acid levels. Thus, shed new light molecular GC-induced metabolism, which are known increase risk obesity, hyperglycemia, diabetes.