ESTROUS CYCLE AND NEUROENDOCRINE/IMMUNE INTERACTIONS

描述（改编自申请人摘要）：本研究的目的 应用是了解神经内分泌和免疫 动情周期调节作用的潜在机制， 性腺激素和性别对免疫能力和肿瘤发展的影响。 免疫系统和神经内分泌系统相互调节。 在 除了性激素分泌外，许多神经内分泌反应，例如， 应激反应，已知是性二态的，因此， 提示免疫和肿瘤的两性异形的潜在机制 易感性 临床观察报告高达三倍 由于肿瘤复发导致的长期死亡率增加， 在高雌激素-低孕激素期间接受乳房切除术的妇女 月经周期的一个阶段。 使用乳腺癌的动物模型 转移，研究人员观察到， 宿主的能力，以防止转移在发情期的 F344大鼠，与高危期同源 报告中的女性。 因此，他们推测， 观察结果可归因于宿主对 乳腺切除术引起的肿瘤扩散，抑制性 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， 其设计有以下三个具体目标：（1） 阐明激素介质的发情周期的影响，他们有 观察到，特别是雌二醇，孕酮， 催乳素;（2）为了验证自然杀伤细胞的改变 (NK)性类固醇或催乳素诱导的细胞活性， 动情周期对转移过程的影响，并研究可能的 这些激素影响NK活性的细胞机制;和（3） 研究和区分性别、长期 暴露于性腺类固醇或催乳素，以及实际年龄 NK细胞活性的功能性下降。 调查人员认为 这些研究的结果将提供重要的新信息， 改进保健战略， 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.