Gastric estrogen directly induces ghrelin expression and production in the rat stomach

Gastric estrogen directly induces ghrelin expression and production in the rat stomach
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DOI:
10.1677/joe.1.06808
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发表时间:
2006-09-01
影响因子:
4
通讯作者:
Sakai, Takafumi
Sakai, Takafumi
中科院分区:
医学2区
文献类型:
--
作者:
Sakata, Ichiro;Tanaka, Toru;Sakai, Takafumi

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胃促生长素是生长激素促分泌受体的内源性配体,主要在胃中产生。胃饥饿素的调节机制尚不清楚。在此,我们报道了在胃中合成的雌激素诱导大鼠胃饥饿素基因的表达和产生。我们建立了Percoll离心富集胃饥饿素细胞的方法,并研究了雌激素和/或其拮抗剂对胃饥饿素表达和产生的影响。雌激素治疗8小时显著增加ghrelin的表达水平,而雌激素受体拮抗剂ICI-182 780完全逆转了这一作用。逆转录- pcr分析表明,雌性大鼠胃中有ER α和芳香化酶的表达。此外,芳香化酶抑制剂4-羟基雄烯二酮(福美斯坦)可显著降低胃糜组织中ghrelin mRNA的表达水平。体内研究显示,手术后3周,去性腺的大鼠胃饥饿素mRNA的表达和产生没有变化。这些结果有力地表明,胃中产生的雌激素直接诱导了雌性和雄性大鼠胃中ghrelin的表达和产生。
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 ER alpha and aromatase are expressed in the female rat stomach. Moreover, treatment with an aromatase inhibitor, 4-hydroxyandrostenedione (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.