Analysis of the brain mechanism regulating the reproductive system using small laboratory animals.

利用小型实验动物分析调节生殖系统的大脑机制。

• 批准号: 06044101
• 负责人: MAEDA Kei-ichiro
• 金额: $ 4.48万
• 依托单位: NAGOYA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06044101/
• 关键词: luteinizing hormone; luteinizing hormone-releasing hormone; glucose; LHRH pulse generator; pituitary; hypothalamus; area postrema; 最後野; 多ニューロン発火活動

The collaboration is on leading conceptual and technological edges of research in reproductive neuroendocrinology. Our research is being driven by fundamental questions relating to nutrition, growth, and reproductive activity for which we do not have answers. For example, we know that the reproductive system is activated at a specific time during growth in animals and that low nutrition retards growth and delays this activation. However, we are completely ignorant about how the brain knows when growth is sufficient to begin the reproductive process. The most basic elements of this mechanism are not yet understood. After puberty, we know that the reproductive system shuts down during periods of low nutrition, but how the brain senses which nutrients are inadequate is uncertain. We believe that answers to such questions will be forthcoming when we better understand how changes in energy metabolism or reserves are sensed by the brain.The participants through complementary skills, approach … More es, and experimental models are attempting to unravel how metabolic signals are sensed by the brain and routed through neural pathways to regulate the specialized neurons which secrete a unique neuropeptide the controls the entire reproductive system. This peptide, gonadotropin-releasing hormone (GnRH) for which the Nobel prize for Medicine was awarded for its discovery two decades ago, is the single-most important reproductive hormone in the body. Without it, reproduction is not possible in any mammalian species thus far studied. The peptide is not secreted into the peripheral circulation and is only measurable in the microcirculation between the hypothalamus and the pituitary gland which it controls. Its pattern of secretion is generally not measurable in small animal models. However, facilitated by the particular location of the microcirculation in the sheep and goat, the pattern of GnRH can be characterized precisely by a special approach in these large animal models which we will use in this collaboration. Moreover, in these models, electrophysiological correlates of GnRH secretion can be analyzed simultaneously to better understand the neural components of its regulation. On the other hand, the rat is invaluable to study pathways of information transmission and sites of regulation because of the well established stereotaxic approaches and molecular technologies available for this widely used model.We have developped a new concept that energy availability strictly controls the reproductive axis in developing and developed animals. Blood glucose level and its availability are the most important factors regulating physiological events and behavior in the reproduction at various phases. Glucose availability may be sensed centrally and peripherally to regulate reproductive functions as well as feeding behavior, but the location of the sensors and the mechanism of sensing are still unknown. Less

这项合作是在生殖神经内分泌学研究的概念和技术前沿。我们的研究是由与营养、生长和生殖活动有关的基本问题推动的，我们对这些问题没有答案。例如，我们知道动物的生殖系统在生长过程中的特定时间被激活，低营养会阻碍生长并延迟这种激活。然而，我们完全不知道大脑是如何知道什么时候生长足够开始生殖过程的。人们还不了解这一机制的最基本要素。青春期过后，我们知道生殖系统会在营养不足的时期关闭，但大脑如何感知哪些营养不足还不确定。我们相信，当我们更好地了解大脑如何感知能量新陈代谢或储备的变化时，这些问题的答案将会随之而来。参与者通过互补技能，接近…更多的ES，以及实验模型正在试图解开代谢信号是如何被大脑感知并通过神经通路来调节专门的神经元的，这些神经元分泌一种独特的神经肽来控制整个生殖系统。这种肽，促性腺激素释放激素(GnRH)，20年前因其发现而获得诺贝尔医学奖，是人体内最重要的生殖激素。没有它，到目前为止所研究的任何哺乳动物物种都不可能繁殖。这种肽不会分泌到外周循环中，只能在它控制的下丘脑和脑下垂体腺之间的微循环中检测到。它的分泌模式在小动物模型中通常是无法测量的。然而，由于绵羊和山羊微循环的特殊位置，GnRH的模式可以通过一种特殊的方法在这些大型动物模型中准确地表征，我们将在这次合作中使用这种方法。此外，在这些模型中，可以同时分析GnRH分泌的电生理相关性，以更好地了解其调节的神经成分。另一方面，大鼠在研究信息传递途径和调控部位方面是非常有价值的，因为这种广泛使用的模型已经建立了完善的立体定位方法和分子技术。我们发展了一个新的概念，即在发育和发育的动物中，能量的可获得性严格控制生殖轴。血糖水平及其可获得性是调节生殖各阶段生理事件和行为的最重要因素。葡萄糖的可获得性可以在中枢和外周感知，以调节生殖功能和摄食行为，但传感器的位置和感知机制仍不清楚。较少

项目成果

Maeda, K.I., Tsukamura, H., Ohkura, S.and Yokoyama, A.: "The LHRH pulse generator : An ultradian pacemaker controlling the hypothalamic hormone secretion." Neuroscience and Biobehavioral Reviews. 19. 427-437 (1995)

Maeda, K.I.、Tsukamura, H.、Ohkura, S. 和 Yokoyama, A.：“LHRH 脉冲发生器：控制下丘脑激素分泌的超电起搏器。”

Maeda, K.-I., Nagatani, S., Estacio, M.A.and Tsukamura, H.: "Novel feedback sites associated with stress-induced suppression of luteinizing hormone secretion in female rats." Cellular and Molecular Neurobiology. 16. 311-324 (1995)

Maeda, K.-I.、Nagatani, S.、Estacio, M.A. 和 Tsukamura, H.：“与应激诱导的雌性大鼠黄体生成素分泌抑制相关的新反馈位点。”

Nagatani, Shoji: "Reduction of glucose availability suppresses pulsatile LH release in female and male rats." Endocrinology. 137. 1166-1170 (1996)

Nagatani, Shoji：“葡萄糖利用率的降低会抑制雌性和雄性大鼠的脉动性 LH 释放。”

Murahashi, Kumiko: "Suppression of LH pulses by restriction of glucose availability is mediated by sensors in the brain stem." Endocrinology. 137. 1171-1176 (1996)

Murahashi、Kumiko：“通过限制葡萄糖可用性来抑制 LH 脉冲是由脑干中的传感器介导的。”

Murahashi, K., Bucholtz, D.C., Nagatani, S., Tsukahara, S., Tsukamura, H., Foster, D.L.and Maeda, K.-I.: "Suppression of LH pulses by restriction of glucose availability is mediated by sensors in the brain stem." Endocrinology. 137. 1171-1176 (1996)

Murahashi, K.、Bucholtz, D.C.、Nagatani, S.、Tsukahara, S.、Tsukamura, H.、Foster, D.L. 和 Maeda, K.-I.：“通过限制葡萄糖可用性来抑制 LH 脉冲是由传感器介导的