Department of Biological Sciences, University of Cincinnati, Cincinnati, OH, United States.
Department of Biological Sciences, University of Cincinnati, Cincinnati, OH, United States.
Gen Comp Endocrinol. 2020 May 15;291:113419. doi: 10.1016/j.ygcen.2020.113419. Epub 2020 Feb 4.
Stress hormones, also known as glucocorticoids, are critical for survival at birth in mammals due at least in part to their importance in lung maturation. However, because air breathing is not always required for amphibian survival and because stress hormones have no known developmental impact except to modulate the developmental actions of thyroid hormone (TH), the requirement for stress hormone signaling during metamorphosis is not well understoodi. Here, we produced a glucocorticoid receptor knockout (GRKO) Xenopus line with a frameshift mutation in the first exon of the glucocorticoid receptor. Induction by exogenous corticosterone (CORT, the frog stress hormone) of the CORT response genes, klf9 (Krüppel-like factor 9, also regulated by TH) and ush1g (Usher's syndrome 1G), was completely abrogated in GRKO tadpoles. Surprisingly, GRKO tadpoles developed faster than wild-type tadpoles until forelimb emergence and then developed more slowly until their death at the climax of metamorphosis. Growth rate was not affected in GRKO tadpoles, but they achieved a smaller maximum size. Gene expression analysis of the TH response genes, thrb (TH receptor beta) and klf9 showed reduced expression in the tail at metamorphic climax consistent with the reduced development rate. These results indicate that glucocorticoid receptor is required for survival through metamorphosis and support dual roles for GR signaling in control of developmental rate.
应激激素，也被称为糖皮质激素，在哺乳动物的出生时对于生存至关重要，这至少部分归因于它们在肺成熟中的重要作用。然而，由于两栖动物的生存并不总是需要空气呼吸，并且应激激素除了调节甲状腺激素（TH）的发育作用之外没有已知的发育影响，因此在变态过程中对应激激素信号的需求还不是很清楚。在这里，我们生产了一种带有糖皮质激素受体（GR）外显子 1 移码突变的糖皮质激素受体敲除（GRKO）爪蟾系。外源皮质酮（CORT，青蛙应激激素）诱导的 CORT 反应基因 klf9（Krüppel 样因子 9，也受 TH 调节）和 ush1g（Usher 综合征 1G）的表达在 GRKO 蝌蚪中完全被阻断。令人惊讶的是，GRKO 蝌蚪的发育速度比野生型蝌蚪快，直到前肢出现，然后发育速度变慢，直到变态高潮时死亡。GRKO 蝌蚪的生长速度不受影响，但它们达到的最大体型较小。TH 反应基因 thrb（TH 受体β）和 klf9 的基因表达分析表明，在变态高潮时尾巴的表达减少，与发育速度降低一致。这些结果表明，糖皮质激素受体是通过变态存活所必需的，并支持 GR 信号在控制发育速度中的双重作用。
