Regulation by calcitonin and glucocorticoids of calcitonin receptor gene expression in mouse osteoclasts.
Regulation by calcitonin and glucocorticoids of calcitonin receptor gene expression in mouse osteoclasts.
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降钙素和糖皮质激素对小鼠破骨细胞中降钙素受体基因表达的调节。
作者：
S. Wada;N. Udagawa;T. Akatsu;N. Nagata;T. Martin;D. Findlay
我们以前研究了调节降钙素（CT）受体（CTR）的糖皮质激素（GC）和CT培养成熟的小鼠破骨细胞样细胞（OCL）。本研究旨在探讨CT和GC在破骨细胞CTR调控中的相互作用及其分子机制。用10（-7）M地塞米松（Dex）处理OCL以时间依赖性方式增加CTR数量，而用10（-9）M鲑鱼CT（sCT）处理则减少CTR数量;两种处理均未改变受体亲和力。地塞米松预处理在一定程度上拮抗了CT诱导的[125 I]sCT特异性结合的降低。地塞米松增加，和sCT预处理降低，sCT响应的腺苷酸环化酶活性与受体结合的变化平行。地塞米松治疗导致CTR信使RNA（mRNA）水平增加，如通过逆转录-PCR评估的，表明CTR数量增加是由从头CTR合成介导的。这种作用是特定的GC和不复制盐皮质激素或性类固醇。用sCT治疗导致CTR mRNA表达的快速和深刻的减少，并且这种减少在一定程度上被Dex预处理延迟。用5，6-二氯-1 β-D-呋喃核糖基苯并咪唑处理OCL，以能够在不存在持续转录的情况下估计mRNA衰减速率。CTR mRNA的稳定性与Dex处理的OCL中的对照值相似，表明Dex的作用可能是由于转录活性的变化。有趣的是，5，6-二氯-1 β-D-呋喃核糖基苯并咪唑的转录抑制作用消除了CT降低CTR mRNA水平的能力，表明CT可能通过增加CTR mRNA衰减速率起作用，并且这种作用需要持续的转录。小鼠CTR mRNA的3 '-非翻译区含有AUUUA基序的四个拷贝，以及其他富含A/U的序列，这些序列已被证明决定其他mRNA转录物的稳定性。稳定性结果与核转录物连续测定的结果一致，这表明用Dex处理增强了转录速率，而CT没有影响。这些结果表明GC和CT通过不同的机制影响CTR表达，并为鉴定所涉及的细胞因子提供了基础。
We previously studied regulation of the calcitonin (CT) receptor (CTR) by glucocorticoid (GC) and CT in cultures of mature mouse osteoclast-like cells (OCLs). The present studies were designed to examine the interaction of CT and GC in regulation of the CTR in osteoclasts and the molecular mechanisms involved. Treatment of OCLs with 10(-7) M dexamethasone (Dex) increased the CTR number in a time-dependent manner, whereas treatment with 10(-9) M salmon CT (sCT) reduced CTR number; neither treatment changed receptor affinity. Dex pretreatment somewhat antagonized the CT-induced reduction in [125I]sCT specific binding. Dex increased, and sCT pretreatment decreased, the sCT-responsive adenylate cyclase activity in parallel with the change in receptor binding. Dex treatment resulted in an increase in CTR messenger RNA (mRNA) levels, as assessed by reverse transcription-PCR, indicating that the increased CTR number was mediated by de novo CTR synthesis. This effect was specific to GCs and was not reproduced by mineralocorticoids or sex steroids. Treatment with sCT resulted in a rapid and profound reduction in CTR mRNA expression, and this reductions was somewhat delayed by Dex pretreatment. OCLs were treated with 5,6-dichloro-1 beta-D-ribofuranosyl benzimidazole to enable estimation of the mRNA decay rates in the absence of ongoing transcription. The stability of CTR mRNA was similar to the control value in Dex-treated OCLs, suggesting that the effect of Dex may be due to changes in transcriptional activity. Interestingly, transcriptional inhibition by 5,6-dichloro-1 beta-D-ribofuranosyl benzimidazole abolished the ability of CT to reduce CTR mRNA levels, suggesting that CT may act by increasing the rate of CTR mRNA decay, and that this effect requires ongoing transcription. The 3'-untranslated region of the mouse CTR mRNA contains four copies of the AUUUA motif, as well as other A/U-rich sequences, which have been shown to determine the stability of other mRNA transcripts. The stability results were consistent with the results of the nuclear transcript run-on assay, which indicated that treatment with Dex enhanced the rate of transcription, whereas CT had no effect. These results show that GC and CT influence CTR expression by distinct mechanisms and provide the basis for identification of the cellular factors involved.
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影响因子：
4.8
作者：
Yamin,M;Gorn,AH;Flannery,MR;Jenkins,NA;Gilbert,DJ;Copeland,NG;Tapp,DR;Krane,SM;Goldring,SR
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Goldring,SR
DOI：
10.1172/jci117634
发表时间：
1995
期刊：
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影响因子：
4.8
作者：
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DOI：
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发表时间：
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期刊：
The Journal of biological chemistry
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通讯作者：
Sadler,JE
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DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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通讯作者：
Malbon,CC