The structure and regulation of the oxytocin receptor
The structure and regulation of the oxytocin receptor
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DOI：
10.1113/eph8602185
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发表时间：
2001-03-01
影响因子：
2.7
通讯作者：
Fuchs, AR
中科院分区：
文献类型：
--
作者：
Ivell, R;Kimura, T;Fuchs, AR
催产素受体（OTR）是一个古老的激素系统的一部分，在不同的门中表达，与急性生殖平滑肌反应有关，如产卵、分娩或泌乳。虽然OTR基因的调控与体内类固醇水平相关，但仍然难以捉摸。似乎有抑制和刺激的影响作用于基础表达的构成模式。然而，我们没有发现任何证据表明性类固醇会直接影响基因转录，或者在蛋白质水平上影响受体本身。在前列腺癌细胞Du145中，我们发现cAMP可以上调OTR基因的转录。为了表征OTR蛋白在体内的表达，我们使用配体印迹法证明，在转染细胞和肌层中，OTR可以以不同的大小表达。此外，在足月的肌层中，免疫组织化学显示每个细胞中OTR蛋白的增加，以及表达OTR的平滑肌细胞的数量的增加，强调围产期变化是个体基因激活事件和总细胞分化的结果。OTR是反映围产期分子变化的有价值的模型系统。当我们了解这个重要的分子是如何被调节的，我们也将在理解出生时控制子宫肌收缩的机制方面有很长的路要走。
The oxytocin receptor (OTR) is part of an ancient hormone system expressed in diverse phyla in relation to acute reproductive smooth muscle responses, such as egg-laying, birth, or milk letdown. The regulation of the OTR gene, while correlating with steroid levels in vivo, remains elusive. There appear to be both inhibitory and stimulatory influences acting upon a constitutive pattern of basal expression. We have found no evidence, however, for an effect of the sex steroids either directly on gene transcription, or on the receptor itself at the protein level. In the prostatic carcinoma cell line Du145, we have shown that up-regulation of the OTR gene transcription can be effected by cAMP. In an attempt to characterize the expression of the OTR protein in vivo, we ha we shown, using ligand-blotting, that the OTR can be expressed at different sizes in transfected cells and in myometrium. Also, in the myometrium at term, immunohistochemistry suggests that there is both an increase in OTR protein per cell, as well as in the number of smooth muscle cells expressing OTR, emphasizing that perinatal changes are the results of both individual gene activation events and gross cellular differentiation. The OTR is a valuable model system reflecting molecular changes in the perinatal period. When we understand how this important molecule is regulated, we will also be a long way towards understanding the mechanisms controlling myometrial contractility at birth.