NEUROPEPTIDE CO-EXPRESSION IN THE HYPOTHALAMUS

下丘脑中的神经肽共表达

• 批准号: 3402075
• 负责人: Paul E. Sawchenko
• 金额: $ 10.73万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-23 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3402075
• 关键词: adrenalectomy; brain metabolism; catecholamines; corticotropin releasing factor; estrogens; experimental brain lesion; gene expression; histochemistry /cytochemistry; homeostasis; hormone regulation /control mechanism; hypophysectomy; hypothalamus; immunofluorescence technique; neural plasticity; neuroanatomy; neuroendocrine system; ovariectomy; steroid hormone; tissue /cell preparation; vasopressins

The proposed neuroanatomical studies are designed to test the hypothesis that alterations in steroid hormone status can effect pronounced changes in the cellular localization, and co-localization, of neuropeptides in the mammalian hypothalamus. Immunohistochemical double-staining methods will be used to assay the responses of biochemically- and functionally-specified pools of neurons in the paraventricular nucleus of the hypothalamus (PVH) to various endocrine manipulations. We have described on adrenal steroid-dependent co-expression corticotropin releasing factor (CRF)- and vasopressin-immunoreactivity (IR) in parvocellular neurosecretory neurons and preliminary studies suggest that the same two peptides may be expressed in magnocellular neurosecretory neurons in estrogen-treated ovariectomized rats. Additional study is required to characterize these phenomena by determining: (i) whether these responses to manipulation of steroid hormone status are specific to CRF- and vasopressin-IR, (ii) the identity of the steroids that mediate these responses, (iii) the site(s) within the brain at which steroids act to influence peptide expression, (iv) the role of neural inputs to the PVH in mediating steroid-dependent and steroid-independent changes in peptide expression, and (v) whether the co-expression of CRF- and vasopressin-IR in parvocellular and magnocellular neurosecretory neurons occur over the course of normal fluctuations in adrenal and ovarian steroid titers. Collectively, these studies should establish the existence of a plasticity in the expression of neuropeptides by neuroendocrine neurons as a function of physiological state. This may prove to be an important organizing principle in hypothalamic circuitry that serves to maintain homeostasis. The peptides in question play well-recognized roles in such essential and health-related processes as the regulation of the cardiovascular system, the protection of the organism from stress and the control of reproductive function.

拟议的神经解剖学研究旨在验证这一假说。 类固醇激素状态的改变会影响 神经肽的细胞定位和共定位 哺乳动物的下丘脑。免疫组织化学双重染色方法将 用于分析生物化学和功能指定的反应 下丘脑室旁核(PVH)的神经元池 不同的内分泌操作。我们已经在肾上腺上描述过 类固醇依赖性促肾上腺皮质激素释放因子(CRF)-和 小细胞神经分泌神经元的加压素免疫反应 初步研究表明，可能表达了相同的两个多肽 雌激素对去卵巢大细胞神经分泌神经元的影响 老鼠。需要更多的研究来描述这些现象的特征 确定：(I)这些对操纵类固醇的反应 激素状态是CRF-和加压素-IR所特有的，(Ii)同一性 在调节这些反应的类固醇中，(Iii)在 类固醇影响多肽表达的大脑，(Iv)作用 下丘脑室旁核神经输入在调节类固醇依赖和 激素非依赖性多肽表达的变化，以及(V)是否 CRF-和加压素-IR在小细胞和巨细胞中的共表达 神经分泌神经元发生在正常波动的过程中 肾上腺和卵巢类固醇效价。总的来说，这些研究应该 证明神经肽表达存在可塑性 由神经内分泌神经元作为生理状态的函数。今年5月 被证明是下丘脑回路的一个重要组织原则 这有助于维持动态平衡。有问题的多肽正在发挥作用 在基本和与健康有关的进程中发挥公认的作用，如 调节心血管系统，保护生物体 来自压力和生殖功能的控制。