Reproduction, Nutrition and Behavior

描述(由申请人提供)：生殖行为是一种典型的动机行为，需要整合多种内部和外部线索才能成功执行。促性腺激素释放激素(GnRH)是一种主要的神经肽，协调生殖条件和行为。然而，许多动物，包括人类，都有第二种形式的GnRH，GnRH-II，它是高度保守的，存在于所有脊椎动物的大脑中(从骨鱼到人类)，由一组独特的神经元产生，但这种肽没有已知的功能。在这一新的应用中，我们将测试新的假设，即这种神经肽，GnRH-II，调节生殖行为，以回应个人的营养状况。我们的假说基于我们的发现：1)脑室内注射GnRH-II，而不是GnRH-I，肽可以激活雌性麝鼠(Suncus Murinus)的生殖行为，但仅限于热量限制的雌性；2)GnRH-II肽的免疫反应性在雌性麝鼠大脑中因繁殖条件和营养状况而异，3)麝鼠脑中含有与GnRH-II肽具有高亲和力的特异性II型GnRH受体，这些受体位于已知控制生殖行为的细胞核中，以及4)GnRH-II注射抑制食物摄取。在我们的实验室里，我们有进行这些研究所需的资源、这种动物模型的经验和技术专业知识。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在一种新的和高度合适的哺乳动物模型系统中的功能。GnRH-II在啮齿类动物脑中的存在尚不清楚，但这种多肽广泛存在于人类和非人类灵长类动物中。通过首先在原始哺乳动物中检测这种神经肽，我们将揭示这种神经肽的保守和可能是最常见的功能。这项工作使用了几种新的方法来剖析GnRH-II、进食和性行为以及营养之间的关系。这一信息很可能为人类GnRH-II多肽的研究提供新的途径。此外，这项工作可能会对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.