Reproduction, Nutrition and Behavior

描述（由申请人提供）：生殖行为是典型的多种动机行为，需要多种内部和外部线索的整合才能成功执行。促性腺激素释放激素（GnRH）是协调生殖状况和行为的主要神经肽。然而，包括人类在内的许多动物都有第二种形式的GnRH，即GnRH- ii，它是高度保守的，存在于所有脊椎动物（硬骨鱼和人类）的动物大脑中，由一组独特的神经元产生，但这种肽没有已知的功能。在这个新的应用中，我们将测试新的假设，即这种神经肽，GnRH-II，根据个体的营养状况调节生殖行为。我们的假设是基于我们的发现；1)脑室内注射GnRH-II肽，而非GnRH-I肽，可激活雌性麝鼠（Suncus murinus）的生殖行为，但仅在热量限制的雌性麝鼠中激活；2)雌性麝鼠脑中GnRH- ii肽的免疫反应性随生殖状态和营养状况的不同而不同；3)麝鼠脑中含有特异性的ii型GnRH受体，这些受体对GnRH- ii肽具有高亲和力，并且这些受体存在于已知的控制生殖行为的细胞核中；4)GnRH- ii注入抑制食物消耗。在我们的实验室里，我们有进行这些研究所需的资源、动物模型的经验和技术专长。我们将结合药理学、免疫细胞化学、外科和行为学方法来建立这个新的研究项目。本文提出的工作将阐明GnRH-II在一种新颖且高度合适的哺乳动物模型系统中的功能。GnRH-II肽在啮齿动物大脑中的存在尚不清楚，但这种肽在人类和非人类灵长类动物中广泛存在。通过首先在原始哺乳动物中检查这种神经肽，我们将揭示这种神经肽的保守和可能最常见的功能。这项工作采用了几种新颖的方法来剖析GnRH-II，喂养和性行为以及营养之间的关系。这可能为人类GnRH-II肽的研究提供新的途径。此外，这项工作可能为饮食失调的生理基础提供见解。

DESCRIPTION (provided by applicant): Reproductive behaviors are typical of a variety of motivated behaviors that require integration of multiple internal and external cues for their successful execution. Gonadotropin releasing hormone (GnRH) is a master neuropeptide that coordinates reproductive condition and behavior. Yet, many animals, including humans, have a second form of GnRH, GnRH-II, which is highly conserved, present in brains of animals from all vertebrate classes (bony fish to humans), produced by a unique group of neurons and yet the peptide has no known function. In this new application we will test the novel hypothesis that this neuropeptide, GnRH-II, modulates reproductive behavior in response to the individual's nutritional status. Our hypothesis is based on our findings that; 1) Intracerebroventricular (icv) administration of GnRH-II, but not GnRH-I, peptide activates reproductive behavior in female musk shrews (Suncus murinus), but only in females experiencing caloric restriction; 2) Immunoreactivity of GnRH-II peptide varies with reproductive condition and nutritional status in female musk shrew brains, 3) Musk shrew brains contain specific type-II GnRH receptors which have a high affinity for GnRH-II peptide, and these receptors are found in nuclei known to control reproductive behavior, and 4) GnRH-II infusions suppress food consumption. In our laboratory we have the needed resources, experience with this animal model, and technical expertise to conduct these studies. We will use a combination of pharmacology, immunocytochemistry, surgical, and behavioral methods to build this new research program. The work proposed here will elucidate the function of GnRH-II in a novel and highly appropriate mammalian model system. The presence of the GnRH-II peptide in rodent brain is unclear, yet this peptide is widespread in human and non-human primates. By examining this neuropeptide first in a primitive mammal we will reveal the conserved and likely the most common function of this neuropeptide. This work employs several novel approaches to dissect the relationship between GnRH-II, feeding and sexual behaviors, and nutrition. It is likely that this information will provide new approaches for the study of GnRH-II peptide in humans. Moreover, this work may provide insights into physiological bases of eating disorders.