Effects of the glucocorticoid clobetasol propionate and its mixture with cortisol and different class steroids in adult female zebrafish

Ecotoxicological effects of glucocorticoids and steroid mixtures in the environment are not sufficiently known. Here we investigate effects of 11-14 days exposure of female zebrafish to the glucocorticoid clobetasol propionate (Clo), cortisol (Cs), their mixture and mixtures with five different class steroids (Clo + triamcinolone + estradiol + androstenedione + progesterone) in liver, brain and gonads. Cs showed little activity, while Clo reduced the condition factor at 0.57 and 6.35 mu g/L. Clo induced differential expression of genes in the liver at 0.07-6.35 mu g/L, which were related to circadian rhythm (per1, nr1d2), glucose metabolism (g6pca, pepck1), immune system response (fkbp 5, socs3, gilz), nuclear steroid receptors (pgr and pxr), steroidogeneses and steroid metabolism (hsd11b2, cyp2k22). Clo caused strong transcriptional down-regulation of vtg. Similar upregulations occurred in the brain for pepck1, fkbp5, socs3, gilz, hsd11b2, and nr1d2a, while cyp19b was down-regulated. Effects of Clo + Cs mixtures were similar to Clo alone. Transcriptional alterations were different in mixtures of five steroids with no alteration of vtg in the liver due to counteraction of Clo and estradiol. Induction of fkbp5 (brain) and sult2st3 (liver) and downregulation of cyp19a (gonads) occurred at 1 mu g/L. Histological effects of the five steroids mixture in gonads were characterized by a decrease of mature oocytes. Our data indicate that effects of steroids of different classes sum up to an overall joint effect driven by the most potent steroid Clo.