NEUROPEPTIDE CO-EXPRESSION IN THE HYPOTHALAMUS

拟议的神经解剖学研究采用免疫组织化学和 杂交组织化学方法来阐明的作用， 特别是激素和神经的影响， 多种神经活性肽的表达， 大鼠下丘脑神经分泌神经元群。 产生促肾上腺皮质激素释放因子的小细胞神经元 启动垂体-肾上腺对压力的反应， 合成肽的大细胞神经分泌神经元 荷尔蒙催产素或加压素（扮演生殖角色） 和身体水分平衡，分别），都已知表达 一些额外的神经肽。 的不同作用 两者都描述了类固醇激素状态的变化 类神经元。 拟议的研究将处理以下问题 问题： 1.非甾体激素对CRF神经元的影响。角色的证据 循环促肾上腺皮质激素甲状腺激素 与哺乳相关的未指明的刺激将被表征 至于它们对共存肽水平的影响，它们的位点 作用和/或是否涉及对基因表达的影响。 2.神经输入在影响脑内肽表达中的作用 CRF神经元脑干投射的作用 儿茶酚胺神经元，海马结构，和基底 前脑介导CRF神经元中的肽动力学，和/或 将评估类固醇在介导反馈作用中的作用。 胺能通路在介导对特异性免疫应答中的作用 还将评价应激模型（出血）。 3. 性腺类固醇对大细胞系统的影响。 我们有 描述了明显的和选择性的影响，操纵 性腺激素状态对共存肽表达的影响 雌性大鼠的大细胞神经分泌神经元。系统性 类固醇替代研究将在性腺切除的 雄性大鼠，以评价 效果。 逆行转运免疫组织化学联合法 方法将被用来确定是否影响是具体的 到大细胞神经元

The proposed neuroanatomical studies employ immunohistochemical and hybridization histochemical methods to clarify the roles of particular hormonal and neural influences in regulating the expression of multiple neuroactive peptides that cohabit neurosecretory neuron populations in the rat hypothalamus. Parvocellular neurons that produce corticotropin-releasing factor for the initiation of pituitary-adrenal responses to stress, and magnocellular neurosecretory neurons that synthesize the peptide hormones oxytocin or vasopressin (which play roles reproduction and body water balance, respectively), are both known to express a number of additional neuropeptides. Differential effects of alterations in steroid hormones status have been described for both class of neurons. The proposed studies will address the following issues: 1. Non-steroidal influences on the CRF neuron. Evidence for roles of circulating corticotropin, thyroid hormones, and as yet unspecified stimuli associated with lactation will be characterized as to their effects on levels of co-existing peptides, their sites of action and/or whether effects on gene expression are involved. 2. Role of neural inputs in influencing peptide expression in the CRF neuron. The roles of projections arising from brainstem catecholamine neurons, the hippocampal formation, and the basal forebrain in mediating peptide dynamics in the CRF neuron, and\or in mediating the feedback effects of steroids will be assessed. The role of aminergic pathways in mediating responses to a specific stress model (hemorrhage) will also be evaluated. 3. Gonadal steroid effects on the magnocellular system. We have described pronounced and selective effects of manipulation of gonadal hormone status on the expression of coexisting peptides in magnocellular neurosecretory neurons of female rats. Systemic steroid replacement studies will be carried out in gonadectomized male rats to evaluate the generality and steroid specificity of the effect. Combined retrograde-transport -immunohistochemical methods will be used to determine whether the effect is specific to magnocellular neurons.