Tsukada S, Ichinose M, Tatematsu M, Tezuka N, Yonezawa S, Kakei N, Matsushima M, Miki K, Kurokawa K, Kageyama T
1st Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Biochem Biophys Res Commun. 1994 Jul 15;202(1):1-9. doi: 10.1006/bbrc.1994.1885.
Adrenalectomy caused a significant decrease in the mucosal level of pepsinogen in the adult rat stomach. This decrease was mainly due to a reduction in the level of the main component of rat pepsinogen isozymogens, namely, Pg1 and in the level of expression of Pg1 mRNA, with a maximal effect being evident 48 hours after operation. Immunohistochemical analysis revealed that the level of expression of Pg1 in the pepsinogen-producing cells was decreased throughout the stomach mucosa and this decrease was especially marked in the immature chief cells located in the glandular neck of the fundic mucosa. Adrenalectomy also increased the proliferation of mucosal cells and suppressed the expression of cathepsin E and class III mucin, markers of differentiated stomach mucosa. All these changes were reversed by hydrocortisone replacement and the extent of the recovery of the level of Pg1 mRNA was dependent on the dose of hydrocortisone, indicating the transcriptional control of the Pg1 gene by hydrocortisone. The observed results suggest that the continuous presence of glucocorticoids is necessary for active transcription of Pg1 gene in fully differentiated stomach mucosa and that glucocorticoids are important regulators of both the function and the morphology of stomach mucosal cells.
肾上腺切除术导致成年大鼠胃黏膜中胃蛋白酶原水平显著降低。这种降低主要是由于大鼠胃蛋白酶原同工酶的主要成分即Pg1水平降低以及Pg1 mRNA表达水平降低，术后48小时效应最为明显。免疫组织化学分析显示，胃蛋白酶原产生细胞中Pg1的表达水平在整个胃黏膜中均降低，且这种降低在位于胃底黏膜腺颈部的未成熟主细胞中尤为明显。肾上腺切除术还增加了黏膜细胞的增殖，并抑制了组织蛋白酶E和III类黏蛋白（分化型胃黏膜的标志物）的表达。所有这些变化均可通过氢化可的松替代得以逆转，且Pg1 mRNA水平恢复的程度取决于氢化可的松的剂量，这表明氢化可的松对Pg1基因具有转录调控作用。观察结果表明，糖皮质激素的持续存在对于完全分化的胃黏膜中Pg1基因的活性转录是必需的，且糖皮质激素是胃黏膜细胞功能和形态的重要调节因子。
