Regulatory Mechanisms by Appetite-Regulating Peptides of the Neuroendocrine System

神经内分泌系统食欲调节肽的调节机制

• 批准号: 12671072
• 负责人: WATANABE Hajime
• 金额: $ 1.79万
• 依托单位: International University of Health and Welfare (2001)Hirosaki University (2000)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671072/
• 关键词: Nutrition; Neuroendocrine function; Leptin; Luteinizing hormone; Prolactin; Appetite-Regulating Peptides; Growth hormone; Melanocortin; 摂食調節ペプチド; Luteinizing hormone; オレキシン

1. Utilizing the push-pull perfusion technique, we investigated the central site at which leptin stimulates the gonadotropin-releasing hormone (GnRH)-luteinizing hormone (LH) system in female rats. We found that leptin acta on both the cell bodies and axon terminals of GnRH neurons to stimulate this neurohormone's release.2. Leptin is also known to stimulate prolactin (PRL) secretion, and we examined its underlying mechanisms. We obtained the data suggesting that α -melanocyte-stimulating hormone (α -MSH) may play a significant role in mediating this hormonal action of leptin, and also that the melanocortin 4 receptor may serve a pivotal role in mediating the α -MSH action.3. We found that nitric oxide in the brain playa a significant role in mediating leptin's facilitatory influences on LH and PRL surges.4. We found that the depressed reproductive function in the obese OLETF female rats is, at least in part, mediated by hyperleptinemia.5. Utilizing the push-pull perfusion method, we examined the mechanism by which leptin stimulates growth hormone (GH) secretion in male rats. We found that growth hormone-releasing factor and somatostatin are important mediators of leptin's actions on GH, but, unexpectedly neurpeptide Y does not seem to play a significant role.6. We examined a possible hormonal action of orexin-A, a potent orexigenic peptide, on reproductive function in female rats. Our results suggest that orexin-A may play a significant role in the generation and maintenance of LH and PRL sures.7. Recent evidence suggests that leukemia inhibitory factor, ciliary neurotrophic factor, and PRL-releasing peptide are also involved in feeding behavior. We found that all three peptides play significant roles in regulating the reproductive system.

1.利用推拉灌流技术，我们研究了瘦素刺激雌性大鼠促性腺激素释放激素（GnRH）-促黄体生成激素（LH）系统的中枢部位。我们发现瘦素作用于GnRH神经元的胞体和轴突终末，刺激这种神经激素的释放.瘦素也被称为刺激催乳素（PRL）分泌，我们研究了其潜在的机制。我们获得的数据表明α -黑素细胞刺激激素（α -MSH）可能在介导瘦素的这种激素作用中起重要作用，并且黑素皮质素4受体可能在介导α -MSH作用中起关键作用.我们发现脑内一氧化氮在介导瘦素对LH和PRL释放的易化作用中起重要作用.我们发现肥胖OLETF雌性大鼠的生殖功能低下至少部分是由高瘦素血症介导的。利用推拉灌流法，我们研究了瘦素刺激雄性大鼠生长激素（GH）分泌的机制。我们发现生长激素释放因子和生长抑素是瘦素对GH作用的重要介质，但出乎意料的是，神经肽Y似乎没有发挥重要作用.我们研究了食欲素-A，一种有效的食欲肽，对雌性大鼠生殖功能的可能的激素作用。我们的研究结果表明，食欲素-A可能在LH和PRL的产生和维持中发挥重要作用。最近的证据表明，白血病抑制因子，睫状神经营养因子和PRL释放肽也参与摄食行为。我们发现这三种肽在调节生殖系统中起重要作用。

项目成果

Watanobe, H.: "Normalization of circulating leptin levels by fasting improves the reproductive function in obese OLETF female rats"Neuropeptides. 35. 45-49 (2001)

Watanobe, H.：“通过禁食使循环瘦素水平正常化可改善肥胖 OLETF 雌性大鼠的生殖功能”神经肽。

Watanobe, H.: "Further evidence for a significant participation of the melanocortin 4 receptor in the preovulatory prolactin surge in the rat"Brain Res Bulletin. 54. 521-525 (2001)

Watanobe, H.：“进一步证明黑皮质素 4 受体在大鼠排卵前催乳素激增中的显着参与”Brain Res Bulletin。

Schioth, H.B.: "Agouti-related peptide prevents steroid-induced luteinizing hormone and prolactin surges in female rats"Neuroreport. 12・4. 687-690 (2001)

Schioth, H.B.：“刺豚鼠相关肽可防止雌性大鼠中类固醇诱导的黄体生成素和催乳素激增”，Neuroreport 12・4 (2001)。

Kohsaka, A.: "A significant participation of orexin-A, a potent orexigenic peptide, in the preovulatory luteinizing hormone and prolactin surges in the rat"Brain Research. 898・1. 166-170 (2001)

Kohsaka，A.：“食欲素-A（一种有效的促食欲肽）在大鼠排卵前黄体生成素和催乳素激增中的重要作用”Brain Research 898·1（2001）。

Lindblom J: "Downregulation of melanocortin receptors in brain areas involved in food intake and reward mechanisms in obese (OLETF) rats"Brain Res. 852. 180-185 (2000)

Lindblom J：“肥胖 (OLETF) 大鼠大脑区域中参与食物摄入和奖赏机制的黑皮质素受体下调”Brain Res。