Transactivational property of chemicals via medaka glucocorticoid receptor 1b using a stable reporter gene assay

The transactivational property of natural and synthetic chemicals via medaka GR1b was investigated after development of a stable cell line for the reporter gene assay. In our study, cortisol was the most potent agonist among the natural corticoids assayed for potency [EC₅₀ (concentration of agonist provoking a response halfway between the baseline and maximum response) 68 nM] and efficacy. Three artificial corticosteroids, namely, dexamethasone [EC₅₀ 16 nM, relative agonistic activity to cortisol (RAA) 144 %], prednisolone (EC₅₀ 81 nM, RAA 116 %) and clobetasol propionate (EC₅₀ 0.10 nM, RAA 220 %), showed strong agonistic activity and were more potent than the original corticoid, F. All synthetic corticoids used in our study were full agonists. Interestingly, melengestrol acetate, a synthetic progestogen, induced luciferase activity in a dose-dependent manner. Based on its EC₅₀ value and RAA of 29 nM and 57 %, respectively, this molecule was assessed as a partial agonist. None of the other steroids and chemicals assayed in our study induced an agonistic response. In conclusion, we successfully developed a stable reporter gene assay that can be used to assess the transactivational property of glucocorticoid-like chemicals toward medaka GR1b.