Kageyama Kazunori, Hanada Komaki, Suda Toshihiro
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Regul Pept. 2010 Jun 8;162(1-3):18-25. doi: 10.1016/j.regpep.2010.02.006. Epub 2010 Feb 19.
Three urocortins (Ucns) are known as members of the corticotropin-releasing factor (CRF) family of peptides and serve as natural ligands for CRF receptors. Ucn1 and Ucn3 exhibit potent effects on the adrenal system via the CRF receptors. This study aimed to explore the regulation and roles of Ucns in the adrenal system using human adrenal carcinoma H295R cells, which express Ucn1, Ucn2, Ucn3, CRF receptor type 1 (CRF(1) receptor), and CRF receptor type 2a (CRF(2a) receptor) mRNA. Forskolin, which stimulates adenylate cyclase and then increases intracellular cAMP production, was shown to transiently decrease Ucn1 and Ucn2 mRNA levels, but increase Ucns 1-3 mRNA levels in H295R cells. Steroidogenic acute regulatory protein, Cyp11beta1, and Cyp11beta2 mRNA levels, and both cortisol and aldosterone secretions were elevated by Ucn1. Cell viability was reduced by both Ucn1 and Ucn3 via the CRF(2) receptor in H295R cells. Ucn1 and Ucn3 increased the expression of the cAMP-response element binding protein and extracellular signal-related kinase (ERK) phosphorylations. The ERK and protein kinase A pathways were involved in Ucn3-decreased cell viability.
三种尿皮质素（Ucns）是促肾上腺皮质激素释放因子（CRF）肽家族的成员，作为CRF受体的天然配体。Ucn1和Ucn3通过CRF受体对肾上腺系统表现出强大作用。本研究旨在利用表达Ucn1、Ucn2、Ucn3、1型CRF受体（CRF(1)受体）和2a型CRF受体（CRF(2a)受体）mRNA的人肾上腺癌细胞H295R，探索Ucns在肾上腺系统中的调节作用和功能。已证明，刺激腺苷酸环化酶进而增加细胞内cAMP生成的福斯高林，可使H295R细胞中Ucn1和Ucn2的mRNA水平短暂降低，但可使Ucns 1 - 3的mRNA水平升高。Ucn1可提高类固醇生成急性调节蛋白、Cyp11β1和Cyp11β2的mRNA水平，以及皮质醇和醛固酮的分泌。在H295R细胞中，Ucn1和Ucn3通过CRF(2)受体降低细胞活力。Ucn1和Ucn3可增加cAMP反应元件结合蛋白的表达以及细胞外信号调节激酶（ERK）的磷酸化。ERK和蛋白激酶A信号通路参与了Ucn3降低细胞活力的过程。
