SEX HORMONE-DEPENDENT CHANGES OF OPIATE SYSTEMS IN RAT BRAIN

大鼠脑中阿片系统的性激素依赖性变化

• 批准号: 5211684
• 负责人: RONALD P HAMMER
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5211684
• 关键词: autoradiography; circadian rhythms; estrogens; estrus; gonads; hormone regulation /control mechanism; hypothalamus; in situ hybridization; laboratory rat; neuroanatomy; neurons; neuropeptides; opioid receptor; preoptic areas; progesterone; receptor expression; reproduction; sex hormones; steroid hormone

The long-term objective of this work is to train MBRS students to conduct research investigations which will elucidate the hypothalamic opioid systems involved in the regulation of reproduction in the rat. In particular, the opioid circuitry of the medial preoptic area will be defined and the effect of gonadal steroid hormone exposure on preoptic mu-opiate receptors and the opioid neurons projecting to this region will be characterized. The specific aims are to (1) define the precise morphology of medial preoptic mu-opiate receptors in relation to the underlying sexually dimorphic neuronal structure, (2) investigate the influence of estrogen and progesterone treatment on the expression of opioid peptides in neurons which supply medial preoptic mu-receptor systems, and (3) examine the mechanism and timing of medial preoptic mu- receptor regulation. Potential imbalances in these systems could affect reproductive hormonal and behavioral processes in humans. Combined in vitro receptor autoradiographic/histological methods will be used to precisely localize hormone-dependent medial preoptic mu-opiate receptors in adult female rats. Once the location of these receptors is known, retrograde tracer/in situ hybridization histochemistry methods will be employed to identify the opioid peptide-expressing neurons which supply these receptors, and the effect of hormone treatment on these identified neurons will be determined using quantitative autoradiographic techniques with cellular resolution. Furthermore, the mechanism of hormonal regulation of receptor level will be examined using protein synthesis blockade at various critical periods in receptor expression, and the normal physiological diurnal variation of these receptors will be determined across the estrous cycle. Characterization of the reciprocal interaction between gonadal steroid hormones and opioid peptides in the preoptic area will ultimately lead to a better understanding of how opioid peptides regulate reproductive behavior and hormonal cyclicity.

这项工作的长期目标是培训MBRS学生进行 研究调查将阐明下丘脑阿片类药物 涉及大鼠繁殖调节的系统。 在 特别，内侧前区域的阿片类电路将是 定义及性腺类固醇激素暴露对前固醇的影响 MU-opiate受体和投射到该区域的阿片类神经元将 被描述。 具体目的是（1）定义精确的 相对于上型MU型受体的形态 潜在的性二态神经元结构，（2）研究 雌激素和孕激素治疗对表达的影响 神经元中的阿片类肽，可提供内侧前MU受体受体 系统，（3）检查内侧前Mu-的机制和时机 受体调节。 这些系统的潜在失衡可能会影响 人类的生殖激素和行为过程。 体外受体放射自显影/组织学方法的组合将是 用于精确定位激素依赖性内侧前MU型 成年雌性大鼠的受体。 一旦这些受体的位置是 已知的逆行示踪剂/原位杂交组织化学方法 将被用来识别表达阿片类肽的神经元 提供这些受体，以及激素治疗对这些受体的影响 确定的神经元将使用定量自显影术确定 具有细胞分辨率的技术。 此外，机制 将使用蛋白质检查受体水平的激素调节 在受体表达的各个关键时期的合成阻滞， 这些受体的正常生理昼夜变化将 在整个发情周期中确定。 表征 性腺类固醇激素与阿片类药物之间的相互作用 前区域中的肽最终将导致更好 了解阿片类肽如何调节生殖行为和 激素循环。