Simopoulos Constantinos, Christodoulou Eirini, Lambropoulou Maria, Tsaroucha Alexandra K, Kakolyris Stylianos, Polychronidis Alexandros, Karayiannakis Anastasios J, Chatzaki Ekaterini
Second Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece.
Neuroendocrinology. 2009;89(3):315-26. doi: 10.1159/000187136. Epub 2008 Dec 19.
The corticotropin-releasing hormone (CRH) system, consisting of CRH, urocortins (Ucns), their receptors CRH(1) and CRH(2), and CRH-binding protein, holds the principal role in mediating the response to stress stimuli. Besides their expression in the brain, CRH neuropeptides and receptors have been found in multiple peripheral sites. We investigated the expression of the CRH system in the human liver, using RT-PCR and immunohistochemistry. Ucn 1 gene transcripts were amplified in all the human liver biopsies examined. Ucn 1 immunoreactivity was localized in hepatocytes. CRH(1) and CRH(2(alpha)) receptor gene expression was also found, and receptor protein had a similar distribution to Ucn 1. Finally, Ucn 1 and CRH receptor expression was demonstrated in hepatic biopsies from a variety of liver pathologies, including primary or metastatic liver carcinoma and cirrhosis. We conclude that the CRH system is expressed by human liver under normal and pathological conditions, Ucn 1 being the major ligand. Further study is required to unfold the biological role of these effectors in liver physiology and pathogenesis, as they may act in an autocrine manner through activation of the CRH receptors expressed locally.
促肾上腺皮质激素释放激素（CRH）系统由CRH、尿皮质素（Ucns）、它们的受体CRH(1)和CRH(2)以及CRH结合蛋白组成，在介导对应激刺激的反应中起主要作用。除了在大脑中的表达外，CRH神经肽和受体还在多个外周部位被发现。我们使用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法研究了CRH系统在人肝脏中的表达。在所检测的所有人类肝脏活检样本中均扩增出了Ucn 1基因转录本。Ucn 1免疫反应性定位于肝细胞中。还发现了CRH(1)和CRH(2(α))受体基因表达，且受体蛋白的分布与Ucn 1相似。最后，在包括原发性或转移性肝癌及肝硬化在内的多种肝脏病变的肝活检样本中证实了Ucn 1和CRH受体的表达。我们得出结论，CRH系统在正常和病理条件下均由人肝脏表达，Ucn 1是主要配体。由于它们可能通过激活局部表达的CRH受体以自分泌方式发挥作用，因此需要进一步研究以揭示这些效应器在肝脏生理和发病机制中的生物学作用。
