In humans, two splice variants of the glucocorticoid receptor (GR) exist: the canonical cc-isoform, and the beta-isoform, which has been shown to have a dominant-negative effect on hGR alpha. Previously, we have established the occurrence of a GR beta-isoform in zebrafish, and in the present study we have investigated the functional role of the zebrafish GR beta (zGR beta). Reporter assays in COS-1 cells demonstrated a dominant negative effect of zGR beta but no such effect was observed in zebrafish PAC2 cells using induction of the 11506 binding protein 5 (fkbp5) gene as readout. Subsequently, we generated a transgenic fish line with inducible expression of zGR beta. Transcriptome analysis suggested transcriptional regulation of genes by zGR beta in this line, but further validation failed to confirm this role. Based on these results, its low expression level and its poor evolutionary conservation, we suggest that the zebrafish GR beta-isoform does not have a functional role in transcriptional regulation. (C) 2017 Elsevier B.V. All rights reserved.