Sterner Zachary R, Buchholz Daniel R
Department of Biological Sciences, University of Cincinnati, Cincinnati, OH 45221, United States.
Department of Biological Sciences, University of Cincinnati, Cincinnati, OH 45221, United States.
Gen Comp Endocrinol. 2022 Jan 1;315:113942. doi: 10.1016/j.ygcen.2021.113942. Epub 2021 Nov 9.
In all vertebrates, thyroid hormone (TH) is critical for normal growth and development. In amphibians, corticosterone (CORT) has no action to advance development by itself but can accelerate development induced by TH. CORT accomplishes this acceleration by increasing tissue sensitivity and responsivity to TH. However, the receptor through which CORT acts to affect TH signaling is not known. To examine the role of the glucocorticoid receptor (GR), GR knockout tadpoles and wild-type tadpoles treated with the GR antagonist, RU486, were exposed to exogenous TH and/or CORT then assayed for gene expression and morphology. We found that levels of the response genes klf9 and thrb induced by TH and associated changes in morphology were decreased in GR knockout tadpoles compared to wild-type tadpoles, suggesting that GR signaling contributes to tissue responsivity to TH. To directly examine the role of GR in TH signaling, we co-treated tadpoles with TH and CORT and found that the TH response gene, thrb, was induced significantly beyond the level induced by TH alone in wild-type tadpoles but not in GR knockout tadpoles or wild-type tadpoles treated with RU486. Similarly, tail and gill resorption was greater in tadpoles treated with CORT plus TH compared to TH alone in wild-type tadpoles but not in tadpoles with impaired GR signaling. Surprisingly, even though GR knockout tadpoles die at metamorphosis, treatment with TH alone enabled their survival. These results demonstrate that signaling through GR is responsible for enhancing TH signaling and is essential for the completion of metamorphosis.
在所有脊椎动物中，甲状腺激素（TH）对正常生长和发育至关重要。在两栖动物中，皮质酮（CORT）本身对促进发育没有作用，但可以加速由TH诱导的发育。CORT通过增加组织对TH的敏感性和反应性来实现这种加速。然而，CORT影响TH信号传导所通过的受体尚不清楚。为了研究糖皮质激素受体（GR）的作用，将GR基因敲除的蝌蚪和用GR拮抗剂RU486处理的野生型蝌蚪暴露于外源性TH和/或CORT，然后检测基因表达和形态。我们发现，与野生型蝌蚪相比，GR基因敲除的蝌蚪中由TH诱导的反应基因klf9和thrb的水平以及相关的形态变化有所降低，这表明GR信号传导有助于组织对TH的反应性。为了直接研究GR在TH信号传导中的作用，我们用TH和CORT共同处理蝌蚪，发现TH反应基因thrb在野生型蝌蚪中被诱导的水平显著超过单独由TH诱导的水平，但在GR基因敲除的蝌蚪或用RU486处理的野生型蝌蚪中并非如此。同样，在野生型蝌蚪中，与单独用TH处理相比，用CORT加TH处理的蝌蚪的尾巴和鳃的吸收更大，但在GR信号传导受损的蝌蚪中并非如此。令人惊讶的是，尽管GR基因敲除的蝌蚪在变态时死亡，但单独用TH处理能使其存活。这些结果表明，通过GR的信号传导负责增强TH信号传导，并且对变态的完成至关重要。
