Regulation o the Hypothalanmo-Pituitary-Gonadal Function by Appetite-Regulating Factors

食欲调节因子对下丘脑-垂体-性腺功能的调节

• 批准号: 14571071
• 负责人: WATANOBE Hajime
• 金额: $ 1.98万
• 依托单位: International University of Health and Welfare
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571071/
• 关键词: Appetite-regulating factors; Endocrine function; Leptin; Prolactin; α-MSH; Cytokine; Growth hormone; Melanocortin; 雌雄差; メラノコルチン-4受容体; 国際情報交換; スウェーデン:イタリア; 性腺機能; LH; GT1-7細胞; GnRH; 受容体

Leptin is an adipocyte-derived hormone serving as an appetite-regulating factor, and furthermore regulates various neuroendocrine functions linking nutrition and endocrine systems. The present research project led to the following novel, data.1.Mechanism underlying the. sex-related difference in plasma leptin concentrations. It is well known that females have higher leptin levels than males in humans and also other mammals, but its underlying mechanism remains elucidated. The present study suggests that the neonatal exposure to androgens in male rats mediates, at least in part, the male-type lower leptin concentrations.2.Mechanism of leptin-induced prolactin secretion. This subject was examined in the present study, and the. following data were obtained. Stimulation of prolactin secretion by leptin is mediated by none of dopamine, serotonin, vasoactive intestinal peptide, prolactin-releasing peptide, or beta-endorphin, and only alpha-melanocyte-stimulating hormone seems to play a signi … More ficant intermediary role by way of the melanocortin 4 receptor in the brain.3.Mechanism of the suppression of the hypothalamo-pituitary-gonadal axis by inflammatory cytokines. It is well established that endotoxemia in bacterial infections induces the suppression of the hypothalamo-pituitary-gonadal axis, but the details of cytokines' roles in this phenomenon are not fully understood. The present study demonstrates that interleukin-1beta and tumor necrosis factor-alpha are almost equipotent in suppressing the release of gonadotropin-releasing hormone from rat hypothalamus, but the involvement of interleukin-6 is insignificant in this regard.4.Role of melanocortin receptors in leptin-induced growth hormone secretion. It has been reported that the melanocortin 4 receptor in the brain mediates the actions of leptin on the hypothalamo-pituitary-thyroid/gonadal/adrenal axes. This study demonstrated that leptin-induced stimulation of growth hormone release is not mediated by either the melanocortin 3 or 4 receptor. Less

瘦素是一种脂肪细胞来源的激素，作为食欲调节因子，还调节连接营养和内分泌系统的各种神经内分泌功能。目前的研究项目产生了以下新颖的数据：1.潜在的机制。血浆瘦素浓度的性别相关差异。众所周知，在人类和其他哺乳动物中，女性的瘦素水平高于男性，但其潜在机制仍有待阐明。本研究表明，雄性大鼠新生期雄激素暴露至少部分介导了雄性型较低瘦素浓度。2.瘦素诱导催乳素分泌的机制。本研究对此主题进行了检验，并且。获得以下数据。瘦素对催乳素分泌的刺激不受多巴胺、血清素、血管活性肠肽、催乳素释放肽或β-内啡肽介导，只有α-黑素细胞刺激激素通过大脑中的黑皮质素4受体发挥重要的中介作用。 3.抑制促乳素分泌的机制 炎症细胞因子影响下丘脑-垂体-性腺轴。众所周知，细菌感染中的内毒素血症会引起下丘脑-垂体-性腺轴的抑制，但细胞因子在这种现象中的作用细节尚不完全清楚。本研究表明，白细胞介素1β和肿瘤坏死因子-α在抑制大鼠下丘脑促性腺激素释放激素的释放方面几乎是等价的，但白细胞介素6的参与在这方面并不显着。4.黑皮质素受体在瘦素诱导的生长激素分泌中的作用。据报道，大脑中的黑皮质素 4 受体介导瘦素对下丘脑-垂体-甲状腺/性腺/肾上腺轴的作用。这项研究表明，瘦素诱导的生长激素释放刺激不是由黑皮质素 3 或 4 受体介导的。较少的

项目成果

Watanobe H, Habu S: "Adrenal glucocorticoids do not mediate impaired reproductive function induced by lipopolysaccharide in rats."Neuroendocrinology. 78. 23-28 (2003)

Watanobe H、Habu S：“肾上腺糖皮质激素不会介导脂多糖诱导的大鼠生殖功能受损。”神经内分泌学。

Watanobe H: "Manipulation of neonatal gonadal steroid milieu and leptin secretion in later life in male and female rats"Regulatory Peptides. 110. 219-224 (2003)

Watanobe H：“雄性和雌性大鼠新生性腺类固醇环境和晚年瘦素分泌的操纵”调节肽。

Watanabe, H.: "Leptin regulates growth hormone-releasing factor, Somatostatin and α-melanocyte-stimulating hormone but not neuropeptide Y release in rat hypothalamus in vivo : Relation with growth hormone secretion"Journal of Neuroscience. 22・14. 6265-627

Watanabe, H.：“瘦素调节大鼠下丘脑体内生长激素释放因子、生长抑素和 α-黑素细胞刺激激素的释放，但不调节神经肽 Y 的释放：与生长激素分泌的关系”《神经科学杂志》22・14。

Watanobe H: "Leptin Regulates Growth Hormone-Releasing Factor, Somatostatin, and α-Melanocyte-Stimulating Hormone But Not Neuropeptide Y Release in Rat Hypothalamus In Vivo : Relation with Growth Hormone Secretion"Journal of Neuroscience. 22. 6265-6271 (2

Watanobe H：“瘦素调节大鼠下丘脑体内生长激素释放因子、生长抑素和 α-黑素细胞刺激激素，但不调节神经肽 Y 释放：与生长激素分泌的关系”神经科学杂志 22. 6265-6271 (2)

Watanobe H: "Pivotal roles of α-melanocyte-stimulating hormone and the melanocortin 4 receptor in leptin stimulation of prolactin secretion in rats"Journal of Neurochemistry. 85. 338-347 (2003)

Watanobe H：“α-黑素细胞刺激激素和黑皮质素 4 受体在大鼠瘦素刺激催乳素分泌中的关键作用”《神经化学杂志》85. 338-347 (2003)。