Makrigiannakis A, Zoumakis E, Margioris A N, Theodoropoulos P, Stournaras C, Gravanis A
Department of Pharmacology, Medical School, University of Crete, Iraklion, Greece.
J Clin Endocrinol Metab. 1995 Jan;80(1):185-9. doi: 10.1210/jcem.80.1.7829610.
CRH is produced by several intrauterine sites, including placenta and desidua, during pregnancy. However, no data are available regarding the presence of CRH in the nonpregnant uterus. We now report that CRH is produced in the epithelial cells of normally cycling human uterus and in an endometrial epithelial cell-derived tumor. Specifically, we have found that: 1) Northern blot hybridization analysis of normal glandular endometrium as well as of Ishikawa human endometrial adenocarcinoma cells showed the presence of the CRH messenger RNA; the size of the transcript seemed to be identical to that present in human placenta and rat hypothalamus; 2) immunoreactive CRH (ir-CRH) was detectable in normal dispersed glandular endometrial cells as well as in the Ishikawa adenocarcinoma cells; 3) gel filtration chromatography of normal glandular endometrial and Ishikawa cell extracts and their culture media showed that most ir-CRH present had the mol wt of the authentic CRH peptide; in addition, a larger form of ir-CRH was also present in both normal and tumoral endometrial epithelial cell extracts; the latter most probably correspondents to CRH precursor molecules; and 4) immunofluorescence staining of CRH in normal glandular endometrial and Ishikawa cells revealed a cytoplasm rich in granules positive for ir-CRH. Our findings suggest that CRH may play an important role in the physiological events taking place within the uterine cavity, since CRH seems to be present in nonpregnant as well as pregnant uteri. Since CRH is expressed in normal endometrial epithelial cells and in an epithelial tumoral cell line, we propose the use of the Ishikawa cell line as a convenient model for the in vitro study of endometrial CRH.
促肾上腺皮质激素释放激素(CRH)在孕期由包括胎盘和蜕膜在内的多个子宫内部位产生。然而,关于非孕子宫中CRH的存在情况尚无数据。我们现在报告,CRH在正常月经周期的人子宫上皮细胞以及一种子宫内膜上皮细胞衍生的肿瘤中产生。具体而言,我们发现:1)对正常腺性子宫内膜以及石川人子宫内膜腺癌细胞进行的Northern印迹杂交分析显示存在CRH信使核糖核酸;转录本的大小似乎与人类胎盘和大鼠下丘脑中的相同;2)在正常分散的腺性子宫内膜细胞以及石川腺癌细胞中可检测到免疫反应性CRH(ir-CRH);3)对正常腺性子宫内膜和石川细胞提取物及其培养基进行凝胶过滤层析显示,存在的大多数ir-CRH具有真实CRH肽的分子量;此外,在正常和肿瘤性子宫内膜上皮细胞提取物中也存在一种更大形式的ir-CRH;后者很可能对应于CRH前体分子;4)对正常腺性子宫内膜和石川细胞中的CRH进行免疫荧光染色显示,富含ir-CRH阳性颗粒的细胞质。我们的发现表明,CRH可能在子宫腔内发生的生理事件中起重要作用,因为CRH似乎在非孕子宫和孕子宫中均存在。由于CRH在正常子宫内膜上皮细胞和上皮肿瘤细胞系中表达,我们建议使用石川细胞系作为体外研究子宫内膜CRH的便捷模型。