Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S
Third Department of Internal Medicine, Miyazaki Medical College, Kiyotake, Japan.
Nature. 2001 Jan 11;409(6817):194-8. doi: 10.1038/35051587.
Ghrelin is an acylated peptide that stimulates the release of growth hormone from the pituitary. Ghrelin-producing neurons are located in the hypothalamus, whereas ghrelin receptors are expressed in various regions of the brain, which is indicative of central-and as yet undefined-physiological functions. Here we show that ghrelin is involved in the hypothalamic regulation of energy homeostasis. Intracerebroventricular injections of ghrelin strongly stimulated feeding in rats and increased body weight gain. Ghrelin also increased feeding in rats that are genetically deficient in growth hormone. Anti-ghrelin immunoglobulin G robustly suppressed feeding. After intracerebroventricular ghrelin administration, Fos protein, a marker of neuronal activation, was found in regions of primary importance in the regulation of feeding, including neuropeptide Y6 (NPY) neurons and agouti-related protein (AGRP) neurons. Antibodies and antagonists of NPY and AGRP abolished ghrelin-induced feeding. Ghrelin augmented NPY gene expression and blocked leptin-induced feeding reduction, implying that there is a competitive interaction between ghrelin and leptin in feeding regulation. We conclude that ghrelin is a physiological mediator of feeding, and probably has a function in growth regulation by stimulating feeding and release of growth hormone.
胃饥饿素是一种酰化肽，可刺激垂体释放生长激素。产生胃饥饿素的神经元位于下丘脑，而胃饥饿素受体则在大脑的各个区域表达，这表明其具有中枢性且尚未明确的生理功能。在此我们表明，胃饥饿素参与下丘脑对能量平衡的调节。脑室内注射胃饥饿素可强烈刺激大鼠进食并增加体重增加。胃饥饿素还能增加生长激素基因缺陷大鼠的进食量。抗胃饥饿素免疫球蛋白G可显著抑制进食。脑室内注射胃饥饿素后，在进食调节至关重要的区域发现了神经元激活标记物Fos蛋白，包括神经肽Y6（NPY）神经元和刺鼠相关蛋白（AGRP）神经元。NPY和AGRP的抗体及拮抗剂可消除胃饥饿素诱导的进食。胃饥饿素增强了NPY基因表达并阻断了瘦素诱导的进食减少，这意味着胃饥饿素与瘦素在进食调节中存在竞争性相互作用。我们得出结论，胃饥饿素是进食的生理介质，可能通过刺激进食和生长激素释放而在生长调节中发挥作用。
