Zhao Zheng, Sakata Ichiro, Okubo Yusuke, Koike Kanako, Kangawa Kenji, Sakai Takafumi
Department of Regulation Biology, Faculty of Science, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan.
J Endocrinol. 2008 Mar;196(3):529-38. doi: 10.1677/JOE-07-0300.
Ghrelin, an endogenous ligand for the GH secretagog receptor, is predominantly produced in the stomach. It has been reported that endogenous ghrelin levels are increased by fasting and decreased after refeeding. It has also been reported that estrogen upregulates ghrelin expression and production and that somatostatin inhibits ghrelin secretion, whereas leptin has a paradoxical effect. Recently, several studies have shown that estrogen, somatostatin, and leptin are produced in the stomach, but the direct effects of these gastric hormones on ghrelin expression in a fasting state remain obscure. In this study, we examined the mRNA expression levels of gastric ghrelin, aromatase (estrogen synthetase), leptin and somatostatin, and concentrations of stomach leptin and portal vein 17beta-estradiol in fasted male rats. After 48 h of fasting, although gastric ghrelin mRNA level was significantly increased, both gastric leptin mRNA level and leptin content were decreased. Further, refeeding of fasted rats resulted in a decrease in ghrelin expression level and an increase in leptin expression level. On the other hand, gastric estrogen and somatostatin levels did not change after fasting. In vitro studies revealed that leptin dose-dependently inhibited ghrelin expression and also inhibited estrogen-stimulated ghrelin expression. Moreover, ghrelin cells were found to be tightly surrounded by leptin cells. RT-PCR analysis clearly showed that long and short forms of the leptin receptor are expressed in the rat stomach. These results strongly suggest that an elevated gastric ghrelin expression level in a fasting state is regulated by attenuated restraint from decreased gastric leptin level.
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。据报道，内源性胃饥饿素水平在禁食时升高，再进食后降低。也有报道称，雌激素上调胃饥饿素的表达和产生，生长抑素抑制胃饥饿素的分泌，而瘦素则具有相反的作用。最近，多项研究表明，雌激素、生长抑素和瘦素在胃中产生，但这些胃激素在禁食状态下对胃饥饿素表达的直接影响仍不清楚。在本研究中，我们检测了禁食雄性大鼠胃中胃饥饿素、芳香化酶（雌激素合成酶）、瘦素和生长抑素的mRNA表达水平，以及胃瘦素和门静脉17β-雌二醇的浓度。禁食48小时后，尽管胃饥饿素mRNA水平显著升高，但胃瘦素mRNA水平和瘦素含量均降低。此外，对禁食大鼠再喂食导致胃饥饿素表达水平降低，瘦素表达水平升高。另一方面，禁食后胃雌激素和生长抑素水平没有变化。体外研究表明，瘦素剂量依赖性地抑制胃饥饿素的表达，也抑制雌激素刺激的胃饥饿素表达。此外，发现胃饥饿素细胞被瘦素细胞紧密包围。RT-PCR分析清楚地表明，大鼠胃中表达瘦素受体的长、短形式。这些结果有力地表明，禁食状态下胃饥饿素表达水平的升高是由胃瘦素水平降低导致的抑制作用减弱所调节的。
