ESTROUS CYCLE AND NEUROENDOCRINE/IMMUNE INTERACTIONS

描述(改编自申请人的摘要)：本报告的目的 应用是了解神经内分泌和免疫学 发情周期调节效应的潜在机制， 性腺激素和性别对免疫能力和肿瘤发生的影响。 免疫系统和神经内分泌系统相互调节。在……里面 除了性激素分泌，许多神经内分泌反应，例如， 压力反应，众所周知是性二态的，因此， 暗示免疫和肿瘤的性别二型性的机制 敏感度。临床观察报告高达三倍 年因肿瘤复发而导致的长期死亡率上升 女性在高雌激素-低孕酮的情况下接受乳房切除术 它们的月经周期处于不同阶段。使用乳腺癌的动物模型 转移后，研究人员观察到 宿主在发情期预防转移的能力 与高危期激素同源的F344大鼠 在女性中有报告。因此，他们假设临床上 观察结果可归因于寄主对 乳房切除引起的肿瘤扩散，一种由抑制引起的减少 性激素对先天免疫的影响。拟议的研究将 使用F344大鼠来解决与人类健康相关的生物医学问题， 它们的设计有以下三个具体目标：(1) 阐明它们对发情周期的影响的激素调节因子 观察到，特别是雌二醇、黄体酮和 催乳素；(2)检验自然杀手中变化的假设 性激素或催乳素诱导的(NK)细胞活性是 发情周期对转移过程的影响及可能的研究 这些激素影响NK活性的细胞机制；以及(3) 研究和区分性别、长期的影响 性腺类固醇或催乳素的暴露，以及实际年龄 关于NK细胞活性的功能性下降。调查人员认为 来自这些研究的发现将提供重要的新的 改善卫生战略的信息，以提高儿童的存活率 癌症患者。

DESCRIPTION (Adapted from applicant's abstract): The objective of this application is to understand the neuroendocrine and immunological mechanisms underlying the modulatory effects of the estrous cycle, gonadal hormones, and gender on immune competence and tumor development. The immune and the neuroendocrine systems regulate each other. In addition to sex hormone secretion, many neuroendocrine responses, e.g., stress responses, are known to be sexually dimorphic, therefore, suggesting mechanisms underlying sexual dimorphism of immunity and tumor susceptibility. Clinical observations report up to a three fold increase in the rate of long-term mortality due to tumor recurrence in women undergoing mastectomy during the high estrogen-low progesterone phase of their menstrual cycle. Using an animal model of breast cancer metastasis, the investigators have observed a large decline in the ability of the host to prevent metastases during estrous phases of the F344 rats that are hormonally homologous to the high risk period reported in women. They therefore hypothesize that the clinical observations are attributable to a decrease in the host resistance to mastectomy-induced tumor dissemination, a decrease caused by suppressive effects of sex hormones on innate immunity. The proposed studies will use the F344 rat to address biomedical issues relevant to human health, and are designed with the following three specific aims: (1) To elucidate hormonal mediators of the estrous cycle effects they have observed, particularly the role of estradiol, progesterone, and prolactin; (2) To test the hypothesis that alteration in natural-killer (NK) cell activity, induced by sex steroids or prolactin, underlies the estrous cycle effect on the metastatic process, and to study possible cellular mechanisms by which these hormones affect NK activity; and (3) to study and distinguish between the effects that gender, long-term exposure to gonadal steroids or prolactin, and chronological age have on functional decline of NK cell activity. The investigators believe that findings from these studies will provide significant new information to improve health strategies for enhancing the survival of cancer patients.