Developmental expression and hormonal regulation of glucocorticoid and thyroid hormone receptors during metamorphosis in Xenopus laevis

Developmental expression and hormonal regulation of glucocorticoid and thyroid hormone receptors during metamorphosis in Xenopus laevis
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DOI:
10.1677/joe.0.1810091
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发表时间:
2004-04-01
影响因子:
4
通讯作者:
Denver, RJ
Denver, RJ
中科院分区:
医学2区
文献类型:
--
作者:
Krain, LP;Denver, RJ

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皮质类固醇,脊椎动物主要的循环应激激素。在两栖动物的变态过程中,甲状腺激素的作用是增强的。环境调节应激激素的产生可能是蝌蚪对幼虫栖息地变化做出反应的一种方式,从而控制变态的时间。甲状腺激素和皮质类固醇通过结构相似的核受体起作用,并且在转录水平上的相互作用可能导致控制变态的共同途径的调节。为了更好地了解皮质类固醇在两栖动物变态中的作用,我们分析了非洲爪蟾蝌蚪脑(间脑)、肠和尾部糖皮质激素受体(GR)mRNA的发育和激素依赖性表达。我们比较了GK的表达模式与甲状腺激素受体β(TRbeta)的表达。为了确定核激素受体表达与配体水平之间的关系,我们还分析了3,5,3 '-三碘甲状腺原氨酸(T3)、甲状腺素和皮质酮(CORT)的全身含量变化。在所有蝌蚪组织中均检测到8、4和2kb的GR转录本,而在胚胎中仅检测到4和2kb的GR转录本。GR mRNA在变态前期在脑中的表达水平较低,但在变态前期显著升高,在整个变态过程中保持恒定水平,在幼蛙中达到最高水平。在整个变态过程中,肠道中GR mRNA水平保持相对稳定,但在尾部增加,在变态高潮时达到最大值。CORT处理后,小肠GR mRNA水平升高,而脑和尾GR mRNA水平无明显变化。在变态过程中,TRbeta mRNA水平在脑、肠和尾中增加,并且通过T-3处理来诱导。对GR(s)和TRs之间可能的交叉调节关系的分析表明,GR mRNA在尾部被外源性T-3(50 nM)上调,但在变性前蝌蚪的大脑中下调。外源性CORT(100 nM)上调肠道中的TRbeta mRNA。本研究结果为核激素受体在变态过程中的组织特异性正、负和交叉调节提供了证据。光滑。CORT与T3对蝌蚪尾部吸收的协同作用可能取决于变态期间GR转录本在该组织中的加速积累,这可能是由血浆甲状腺激素滴度升高驱动的。
Corticosteroids, the primary circulating vertebrate stress hormones. are known to potentiate the actions of thyroid hormone in amphibian metamorphosis. Environmental modulation of the production of stress hormones may be one way that tadpoles respond to variation in their larval habitat, and thus control the timing of metamorphosis. Thyroid hormone and corticosteroids act through structurally similar nuclear receptors, and interactions at the transcriptional level could lead to regulation of common pathways controlling metamorphosis. To better understand the roles of corticosteroids in amphibian meta-morphosis we analyzed the developmental and hormone-dependent expression of glucocorticoid receptor (GR) mRNA in the brain (diencephalon), intestine and tail of Xenopus laevis tadpoles. We compared the expression patterns of GK with expression of thyroid hormone receptor beta (TRbeta). In an effort to determine the relationship between nuclear hormone receptor expression and levels of ligand, we also analyzed changes in whole-body content of 3,5,3'-triiodothyronine (T3), thyroxine, and corticosterone (CORT). GR transcripts of 8, 4 and 2 kb were detected in all tadpole tissues, but only the 4 and 2 kb transcripts could be detected in embryos. The level of GR mRNA was low during premetamorphosis in the brain but increased significantly during prometamor-phosis, remained at a constant level throughout metamor-phosis, and increased to its highest level in the juvenile frog. GR mRNA level in the intestine remained relatively constant, but increased in the tail throughout metamorphosis, reaching a maximum at metamorphic climax. The level of GR mRNA was increased by treatment with CORT in the intestine but not in the brain or tail. TRbeta mRNA level increased in the brain, intestine and tail during metamorphosis and was induced by treatment with T-3. Analysis of possible crossregulatory relationships between GR(s) and TRs showed that GR mRNA was upregulated by exogenous T-3 (50 nM) in the tail but downregulated in the brain of premetamorphic tadpoles. Exogenous CORT (100 nM) upregulated TRbeta mRNA in the intestine. Our findings provide evidence for tissue-specific positive, negative and crossregulation of nuclear hormone receptors during metamorphosis of X. laevis. The synergy of CORT with T3 on tadpole tail resorption may depend on the accelerated accumulation of GR transcripts in this tissue during metamorphosis, which may be driven by rising plasma thyroid hormone titers.