Localization and gestation-dependent pattern of corticotrophin-releasing factor receptor subtypes in ovine fetal distal colon.
Localization and gestation-dependent pattern of corticotrophin-releasing factor receptor subtypes in ovine fetal distal colon.
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绵羊胎儿远端结肠促肾上腺皮质激素释放因子受体亚型的定位和妊娠依赖性模式。
DOI：
10.1111/j.1365-2982.2008.01209.x
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Ross,MG
中科院分区：
文献类型：
--
作者：
Lakshmanan,J;Magee,TR;Richard,JD;Liu,GL;Salido,E;Sugano,SK;Ferrini,M;Ross,MG
经常观察到胎粪排出与胎儿-母体应激因素（如缺氧和感染）相关，但触发机制尚不清楚。我们推测，妊娠期促肾上腺皮质激素释放因子（CRF）受体的差异调节在决定胎儿对足月时子宫胎粪通过中应激诱导的易感性方面起重要作用。我们研究了从极早产到足月妊娠的绵羊胎儿远端结肠段中1型CRF受体（CRF-R1）（胃肠动力刺激剂）和II型CRF受体（CRF-R2）（胃肠动力抑制剂）的神经支配模式。CRF-R1和CRF-R2受体均存在于所有胎龄的胎儿远端结肠段的粘膜肌层以及纵向和环形平滑肌层中。定量图像分析表明，从极早产到足月，粘膜肌层中的CRF-R1受体免疫反应性增加42%，纵向平滑肌层中增加30%。相比之下，在足月时，粘膜肌层以及纵向和环形平滑肌层中的CRF‐R2受体免疫反应性分别下降了38%、55%和51%。足月时肠神经节的百分比和表达CRF-R1受体的肠神经元的数量较高。Western印迹分析鉴定了235和50 kDa分子种类的CRF-R1受体和37和28 kDa分子种类的CRF-R2受体。 总之，我们推测，随着妊娠的进展，肌间平滑肌单位中CRF-R2受体丰度下调，同时CRF-R1受体水平升高，使结肠运动对应激源的反应敏感。
Meconium passage is frequently observed in association with feto‐maternal stress factors such as hypoxia and infection, but the triggering mechanism is unknown. We hypothesize that differential regulation of corticotrophin‐releasing factor (CRF) receptors during gestation play an important role in determining the susceptibilities of the fetus to stress‐inducedin uteromeconium passage at term. We examined the innervation patterns of CRF‐receptor type 1 (CRF‐R1), a stimulator of gastrointestinal motility and CRF‐receptor type II (CRF‐R2), an inhibitor of gastrointestinal motility in ovine fetal distal colonic segments from very preterm to term gestation. Both CRF‐R1 and CRF‐R2 receptors were present in muscularis mucosa as well as in longitudinal and circular smooth muscle layers in fetal distal colonic segments at all gestational ages. Quantitative image analysis indicated a 42% increase in CRF‐R1 receptor immunoreactivity in muscularis mucosa and a 30% in longitudinal smooth muscle layers from very preterm to term. In contrast, CRF‐R2 receptor immunoreactivity in muscularis mucosa as well as in longitudinal and circular smooth muscle layers decreased by 38%, 55% and 51%, respectively, at term. The percentage of enteric ganglia and the number of enteric neurons expressing CRF‐R1 receptors were high at term. Western blot analysis identified 235 and 50 kDa molecular species of CRF‐R1 receptors and 37 and 28 kDa molecular species of CRF‐R2 receptors. In summary, we speculate that downregulation of CRF‐R2 receptor abundance with concurrent increases in CRF‐R1 receptor levels in myenteric‐smooth muscle unit with advancing gestation sensitizes the colonic motility responses to stressors.