Zhao Zheng, Sakai Takafumi
Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan.
World J Gastroenterol. 2008 Nov 7;14(41):6306-11. doi: 10.3748/wjg.14.6306.
Ghrelin was isolated as an endogenous ligand for the GH secretagogue receptor from the rat stomach. Although physiological effects of ghrelin have been revealed by numerous studies, the regulation of stomach ghrelin remains obscure, and the factor that directly regulates ghrelin expression and production has not been identified. Here, we show some data regarding the characteristic features of ghrelin cells and the regulation of stomach ghrelin. In the gastrointestinal tract, ghrelin cells were identified as opened- and closed-type cells, and it was found that the number of ghrelin cells decreased from the stomach to the colon. The postnatal change in number of ghrelin cells in the stomach showed a sexually dimorphic pattern, indicating a role of estrogen in the regulation of stomach ghrelin. In vitro studies revealed that estrogen stimulated both ghrelin expression and production and that treatment with formestane, an aromatase (estrogen synthetase) inhibitor, decreased ghrelin expression level. On the other hand, leptin was found to inhibit both basal and estrogen-stimulated ghrelin expression. Moreover, both aromatase mRNA-expressing cells and leptin cells were found to be located close to ghrelin cells in the gastric mucosa. Furthermore, we found an inverse relationship between gastric ghrelin and leptin levels in a fasting state, and we revealed relative changes in expression of gastric ghrelin, estrogen and leptin in the postnatal rats. We propose that gastric estrogen and leptin directly regulate stomach ghrelin and that the balance control through gastric estrogen and leptin contributes to the altered ghrelin expression level in some physiological states.
胃饥饿素是从大鼠胃中分离出来的生长激素促分泌素受体的内源性配体。尽管众多研究已揭示了胃饥饿素的生理作用，但其在胃中的调节机制仍不清楚，且直接调节胃饥饿素表达和产生的因子尚未明确。在此，我们展示了一些关于胃饥饿素细胞的特征以及胃饥饿素调节的相关数据。在胃肠道中，胃饥饿素细胞被鉴定为开放型和封闭型细胞，并且发现胃饥饿素细胞的数量从胃到结肠逐渐减少。胃中胃饥饿素细胞数量的出生后变化呈现出性别二态性模式，表明雌激素在胃饥饿素的调节中发挥作用。体外研究表明，雌激素可刺激胃饥饿素的表达和产生，而使用芳香化酶（雌激素合成酶）抑制剂福美坦处理可降低胃饥饿素的表达水平。另一方面，发现瘦素可抑制基础状态和雌激素刺激下的胃饥饿素表达。此外，在胃黏膜中发现表达芳香化酶mRNA的细胞和瘦素细胞均位于胃饥饿素细胞附近。此外，我们发现禁食状态下胃饥饿素与瘦素水平呈负相关，并揭示了出生后大鼠胃饥饿素、雌激素和瘦素表达的相对变化。我们提出，胃雌激素和瘦素直接调节胃饥饿素，并且通过胃雌激素和瘦素的平衡控制有助于在某些生理状态下改变胃饥饿素的表达水平。
