Sakata Ichiro, Tanaka Toru, Yamazaki Mami, Tanizaki Takashi, Zheng Zhao, Sakai Takafumi
Department of Regulation Biology, Faculty of Science, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan.
J Endocrinol. 2006 Sep;190(3):749-57. doi: 10.1677/joe.1.06808.
Ghrelin, an endogenous ligand for the GH secretagogue receptor, is predominantly produced in the stomach. Little is known about the regulation mechanism of gastric ghrelin. Here, we report that estrogen synthesized in the stomach induces rat gastric ghrelin gene expression and production. We established a gastric ghrelin cell enrichment method using Percoll centrifugation and then studied the effect of estrogen and/or its antagonist on ghrelin expression and production. Treatment with estrogen for 8 h significantly increased the level of ghrelin expression, and ICI-182 780, an estrogen receptor (ER) antagonist, completely reversed this effect. Reverse transcriptase-PCR analysis clearly showed that ERalpha and aromatase are expressed in the female rat stomach. Moreover, treatment with an aromatase inhibitor, 4-hydro-xyandrostenedione (formestane), significantly decreased the level of ghrelin mRNA expression in minced stomach tissue. In vivo studies revealed that the ghrelin mRNA expression and production did not change in gonadectomized rat 3 weeks after surgery. These results strongly suggest that estrogen produced in the stomach directly induces ghrelin expression and production in both female and male rat stomachs.
胃饥饿素是生长激素促分泌素受体的内源性配体，主要在胃中产生。目前对胃饥饿素的调节机制知之甚少。在此，我们报告胃中合成的雌激素可诱导大鼠胃饥饿素基因表达及产生。我们利用聚蔗糖-泛影葡胺离心法建立了胃饥饿素细胞富集方法，然后研究雌激素和/或其拮抗剂对胃饥饿素表达及产生的影响。用雌激素处理8小时可显著提高胃饥饿素表达水平，而雌激素受体（ER）拮抗剂ICI-182 780可完全逆转这一效应。逆转录聚合酶链反应分析清楚地表明，ERα和芳香化酶在雌性大鼠胃中表达。此外，用芳香化酶抑制剂4-羟基雄烯二酮（福美司坦）处理可显著降低切碎胃组织中胃饥饿素mRNA表达水平。体内研究显示，去势大鼠术后3周胃饥饿素mRNA表达及产生未发生变化。这些结果有力地表明，胃中产生的雌激素可直接诱导雌性和雄性大鼠胃中胃饥饿素的表达及产生。
