Molecular mechanisms of corticosteroid synergy with thyroid hormone during tadpole metamorphosis.
Molecular mechanisms of corticosteroid synergy with thyroid hormone during tadpole metamorphosis.
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DOI：
10.1016/j.ygcen.2010.03.014
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发表时间：
2010-09-01
影响因子：
2.7
通讯作者：
Denver, Robert J.
中科院分区：
文献类型：
--
作者：
Bonett, Ronald M.;Hoopfer, Eric D.;Denver, Robert J.
皮质类固醇(CS)与甲状腺激素(TH)协同作用加速两栖动物的变态。早期的研究表明，CS增加了蝌蚪尾部核3，5，3‘-三碘甲状腺原氨酸(T3)的结合量，并增加了蝌蚪组织中5’脱碘酶的活性，增加了甲状腺激素(T4)生成T3的能力。在本研究中，我们利用蝌蚪尾部外植体培养、变态前期蝌蚪和青蛙组织培养细胞(XTC-2和XLT-15)，通过分析参与TH和CS信号转导的关键基因的表达，研究了CS与TH的协同作用。在100 nm处用T3处理尾部外植体，而在10 nM时不用T3处理尾部外植体，导致尾部退化。皮质酮(CORT)在三个剂量(100,500,3400 nm)对小鼠无作用或增加尾巴大小。T310 NM加CORT引起尾部退缩，与100 NMT3时相似。甲状旁腺激素受体β(Trpβ)基因在T3和皮质醇联合作用下，在尾部外植体、尾部和脑内以及组织培养细胞中协同上调。在体内，T3和CORT诱导尾部外植体和尾部5‘脱碘酶2(D2)mRNA的活化。甲状腺激素增加糖皮质激素(GR)和盐皮质激素受体(MR)mRNAs的表达。我们的发现支持TH和CS在变态过程中的协同作用发生在TR、β和D2基因的表达水平，从而增强了组织对TH的敏感性。同时，TH通过上调GR和MR来增强组织对TH的敏感性。环境应激源可以部分地通过CS增强蝌蚪组织对TH作用的反应来调节蝌蚪变态的时间。
Corticosteroids (CS) act synergistically with thyroid hormone (TH) to accelerate amphibian metamorphosis. Earlier studies showed that CS increase nuclear 3,5,3′-triiodothyronine (T3) binding capacity in tadpole tail, and 5′ deiodinase activity in tadpole tissues, increasing the generation of T3 from thyroxine (T4). In the present study we investigated CS synergy with TH by analyzing expression of key genes involved in TH and CS signaling using tadpole tail explant cultures, prometamorphic tadpoles, and frog tissue culture cells (XTC-2 and XLT-15). Treatment of tail explants with T3 at 100 nM, but not at 10 nM caused tail regression. Corticosterone (CORT) at three doses (100, 500, 3400 nM) had no effect or increased tail size. T3 at 10 nM plus CORT caused tails to regress similar to 100 nM T3. Thyroid hormone receptor beta (TRβ) mRNA was synergistically upregulated by T3 plus CORT in tail explants, tail and brain in vivo, and tissue culture cells. The activating 5′ deiodinase type 2 (D2) mRNA was induced by T3 and CORT in tail explants and tail in vivo. Thyroid hormone increased expression of glucocorticoid (GR) and mineralocorticoid receptor (MR) mRNAs. Our findings support that the synergistic actions of TH and CS in metamorphosis occur at the level of expression of genes for TRβ and D2, enhancing tissue sensitivity to TH. Concurrently, TH enhances tissue sensitivity to CS by upregulating GR and MR. Environmental stressors can modulate the timing of tadpole metamorphosis in part by CS enhancing the response of tadpole tissues to the actions of TH.
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影响因子：
4.8
作者：
Bagamasbad, Pia;Howdeshell, Kembra L.;Denver, Robert J.
通讯作者：
Denver, Robert J.
影响因子：
4.8
作者：
Becker, KB;Stephens, KC;Galton, VA
通讯作者：
Galton, VA
影响因子：
4.8
作者：
Furlow, JD;Kanamori, A
通讯作者：
Kanamori, A
DOI：
10.1073/pnas.93.5.1924
发表时间：
1996-03-05
影响因子：
11.1
作者：
Brown, DD;Wang, Z;Pinder, A
通讯作者：
Pinder, A
影响因子：
4.8
作者：
Bonett, Ronald M.;Hu, Fang;Denver, Robert J.
通讯作者：
Denver, Robert J.