Institut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Université Montpellier, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France.
UMR Hydrosciences Montpellier, Université de Montpellier, Montpellier, France.
Front Endocrinol (Lausanne). 2023 Aug 15;14:1235501. doi: 10.3389/fendo.2023.1235501. eCollection 2023.
The action of environmental steroids on the human glucocorticoid receptor (hGR) has been pointed out with the risk to impair physiological immune and metabolic processes regulated by this nuclear receptor. However, there is still a lack of mechanistic information regarding their ability to interact with GR in aquatic species.
To investigate ligand activation differences between hGR and zebrafish GR (zfGR), we tested several natural and synthetic steroids using reporter cell lines expressing hGR or zfGR.
Almost all the glucocorticoids tested (dexamethasone, cortisol, bimedrazol, medrol, cortivazol and fluticasone) are agonists of the two receptors with similar potencies. The dissociated glucocorticoids, RU24782 and RU24858 are agonists of both zfGR and hGR but with a better potency for the latter. On the other hand, the synthetic glucocorticoid forbimenol and the mineralocorticoid aldosterone are agonist on hGR but antagonist on zfGR. The other steroids tested, androgens and progestins, are all antagonists of both GRs with equal or lower potency on zfGR than on hGR. Surprisingly, the lower efficacy and potency on zfGR of aldosterone, forbimenol and the dissociated glucocorticoids is not related to their affinity for the receptors which would suggest that it could be related to less efficacious recruitment of coactivators by zfGR compared to hGR.
环境甾体对人类糖皮质激素受体（hGR）的作用已被指出，可能会损害该核受体调节的生理免疫和代谢过程。然而，关于它们与水生物种中 GR 相互作用的能力，仍然缺乏机制信息。
为了研究 hGR 和斑马鱼 GR（zfGR）之间配体激活的差异，我们使用表达 hGR 或 zfGR 的报告细胞系测试了几种天然和合成甾体。
几乎所有测试的糖皮质激素（地塞米松、皮质醇、比美莫司、美卓乐、考替唑和氟替卡松）都是两种受体的激动剂，具有相似的效力。分离的糖皮质激素 RU24782 和 RU24858 是 zfGR 和 hGR 的激动剂，但对后者的效力更好。另一方面，合成的糖皮质激素氟米龙和盐皮质激素醛固酮是 hGR 的激动剂，但 zfGR 的拮抗剂。其他测试的甾体，雄激素和孕激素，都是两种 GR 的拮抗剂，对 zfGR 的效力与对 hGR 的效力相等或更低。令人惊讶的是，醛固酮、氟米龙和分离的糖皮质激素在 zfGR 上的效力和效力较低与它们对受体的亲和力无关，这表明这可能与 zfGR 比 hGR 更有效地募集共激活剂有关。
