Studies on novel peptide hormones in the pathophy siology of obesity and hypertension

肾上腺髓质素是一种多功能多肽，具有血管扩张活性、抗氧化应激等作用。艾尔首次表明肾上腺髓质素在脂肪细胞和一种脂肪因子中表达。脂肪细胞有两种上调和下调肾上腺髓质素表达的机制。我们已经证明，肾上腺髓质素基因启动子中的ADRE-AR负责抑制肾上腺髓质素的表达，而Sp1结合部位是诱导肾上腺髓质素表达的位点。此外，Sp1和AP-2可能为复合体，作用于基因启动子，刺激肾上腺髓质素基因表达的诱导。艾尔建立了一种新的肾上腺髓质素相关肽--肾上腺髓质素2的放射免疫分析方法。高桥编辑。艾尔已发现肾上腺髓质素在大脑中的表达，包括下丘脑、垂体、心脏、肾脏和肾上腺。肾上腺髓质素2在脑下垂体和肾脏中的含量特别高。免疫细胞化学研究表明，肾上腺髓质素2在心包脂肪组织中表达。肾上腺髓质素和肾上腺髓质素2在肾上腺和肾上腺肿瘤中均有表达，提示这两种多肽参与了肾上腺肿瘤的病理生理过程。在Ohasama的研究中，我们获得的数据表明肾上腺髓质素2基因的某个基因多态性与高血压的发生有关，脂肪细胞分泌的肾上腺髓质素可能对代谢综合征的并发症具有保护作用。我们希望继续研究脂肪细胞中的肾上腺髓质素，以开发一种治疗肥胖、高血压和糖尿病的新策略。

Adrenomedullin is a multifunctional peptide with vasodilator activity, anti-oxidative stress action, etc.Takahashi ed. al. have shown for the first time that adrenomedullin is expressed in adipocytes and one of the adipokines. Adipocytes have two mechanisms for up-regulation and down-regulation of the adrenomedullin expression. We have shown that the ADRE-AR in the adrenomedullin gene promoter is responsible for the suppression of the adrenomedullin expression, and the Sp1 binding site is for the induction. Furthermore, Sp1 and AP-2 may for the complex, which acts on the gene promoter and stimulate the induction of the adrenomedullin gene expression.Takahashi ed. al. developed a specific radioimmunoassay for adrenomedullin 2, a novel adrenomedullin-related peptide. Takahashi ed. al. have shown the expression of adrenomedullin in the brain including hypothalamus, pituitary, heart, kidney and adrenal gland. Particularly high concentrations of adrenomedullin 2 were found in the pituitary and kidney. Immunocytochemical studies have shown that adrenomedullin 2 is expressed in the pericardial adipose tissue. Adrenomedullin and adrenomedullin 2 were expressed in the adrenal gland and adrenal tumors, suggesting that these two peptides are involved in the pathophysiology of adrenal tumors. We have obtained data which suggest that a certain gene polymorphysm of the adrenomedullin 2 gene is associated with the occurrence of hypertension in the Ohasama study.Adrenomedullins secreted by adipocytes may protect the complications of the metabolic syndrome. We hope to continue to study adrenomedullins in the adipocyte in order to develop a novel strategy for obesity, hypertension and diabetes mellitus.