LPGP, INRA, Campus de Beaulieu, 35042 Rennes, France.
Gen Comp Endocrinol. 2013 Dec 1;194:152-61. doi: 10.1016/j.ygcen.2013.09.011. Epub 2013 Sep 29.
Cortisol is a pleiotropic glucocorticoid hormone that acts through the intracellular glucocorticoid receptors (GR). Cortisol affects many important biological functions in mammals, including immune function, behavior, stress, metabolism, growth and organogenesis. In fishes, cortisol has an additional function in the osmoregulatory activity of ionocytes (ICs). Although much progress has been made toward understanding cortisol action at the levels of adult osmoregulatory tissues, the developmental functions of cortisol and its receptors in ICs remain to be clarified. We first analyzed the total contents of both cortisol and corticosteroid receptor mRNAs (GR1, GR2 and MR) during medaka development. Although low levels of cortisol were detected during development of the medaka embryo, maternal GR1, GR2 and MR transcripts were detected at higher levels than zygotic transcripts. We investigated the effect of exogenous cortisol on IC number during medaka embryogenesis. We observed that cortisol treatment induced an earlier expansion of the IC population but did not modify the final IC number. Using functional genomic approaches, we also tested the involvement of GR1, GR2 and mineralocorticoid receptor (MR) in IC development by systematic knock-down with translation-blocking morpholinos. Only GR2 knock-down led to a reduction of the total number of ICs in the epidermis. In addition, a GR2 splice-blocking morpholino did not have any effect on the biogenesis of ICs, underscoring the importance of maternally inherited GR2 mRNAs. We propose that maternal GR2, but not GR1 or MR, is a major pathway in the IC biogenesis in medaka most likely through cortisol activation, and that cortisol exposition fine-tunes their developmental timing. These findings provide a framework for future research on the regulatory functions of corticosteroids in euryhaline fishes and provide medaka as an advantageous model to further elucidate the underlying molecular regulatory mechanisms of IC development.
皮质醇是一种多功能的糖皮质激素，通过细胞内糖皮质激素受体（GR）发挥作用。皮质醇影响哺乳动物的许多重要生物学功能，包括免疫功能、行为、应激、代谢、生长和器官发生。在鱼类中，皮质醇在离子细胞（IC）的渗透调节活动中具有额外的功能。尽管在理解成年渗透调节组织中皮质醇的作用方面已经取得了很大进展，但皮质醇及其受体在 IC 中的发育功能仍有待阐明。我们首先分析了在斑马鱼发育过程中皮质醇和糖皮质激素受体 mRNA（GR1、GR2 和 MR）的总含量。虽然在斑马鱼胚胎发育过程中检测到低水平的皮质醇，但母体 GR1、GR2 和 MR 转录本的水平高于合子转录本。我们研究了外源性皮质醇对斑马鱼胚胎发生过程中 IC 数量的影响。我们观察到皮质醇处理诱导 IC 群体更早扩张，但不改变最终 IC 数量。通过功能基因组方法，我们还通过翻译阻断型 morpholino 对 GR1、GR2 和盐皮质激素受体（MR）在 IC 发育中的参与进行了系统敲低，以测试它们的参与情况。只有 GR2 敲低导致表皮中 IC 总数减少。此外，GR2 剪接阻断型 morpholino 对 IC 的生物发生没有任何影响，这突显了母体遗传的 GR2 mRNA 的重要性。我们提出，母体 GR2 而不是 GR1 或 MR 是斑马鱼 IC 发生的主要途径，可能通过皮质醇激活，皮质醇暴露精细调节它们的发育时间。这些发现为研究皮质甾类激素在广盐性鱼类中的调节功能提供了一个框架，并为进一步阐明 IC 发育的潜在分子调节机制提供了斑马鱼作为有利模型。
