OVARIAN TUMOR NECROSIS FACTOR

描述(改编自申请人的摘要)： 在本申请中提出的研究是为了阐明肿瘤的作用 大鼠卵泡发育和闭锁中的肿瘤坏死因子一个 抗人重组肿瘤坏死因子抗体已被用于揭示卵巢 颗粒细胞是肿瘤坏死因子的来源。人类肿瘤坏死因子被发现能刺激 卵泡孕酮的体外产生。在本报告中提出的研究 应用将集中在肿瘤坏死因子是否改变健康和健康人的类固醇合成 闭锁卵泡以确定肿瘤坏死因子是否可能是 卵泡闭锁的发病。利用体内和体外实验 卵泡闭锁模型及I125-肿瘤坏死因子与正常和闭锁的结合 卵泡将被确定。在补钠过程中将防止闭锁 苯巴比妥对催乳素致大鼠排卵延迟的影响 肿瘤坏死因子对卵泡类固醇激素生成的影响及与I125-肿瘤坏死因子的结合 将对卵泡进行评估。体内外源性肿瘤坏死因子对血管内皮细胞的影响 将测定健康卵泡的形态和类固醇生成。 计划中的几项研究集中在肿瘤坏死因子的产生是否可以 在体内和体外均受激素调节。自肿瘤坏死因子首次出现以来 在胃窦形成过程中，假设雌激素、卵泡刺激素(和 可能是黄体生成素)调节其生产。此外，肿瘤坏死因子对血管内皮细胞的影响 颗粒细胞的体外增殖是人们特别感兴趣的。从Rate开始 颗粒细胞在体外分裂很差，这可能是 肿瘤坏死因子的产生对它们的生长起到了负面调节作用。因此， 颗粒细胞将在有抗肿瘤坏死因子存在的情况下生长，以便 确定他们的增长是否得到增强。发现肿瘤坏死因子是 在大鼠、牛和人的卵巢中的存在表明了一种 肿瘤坏死因子在其功能中的作用。实验证明，肿瘤坏死因子可以减少 肿瘤生长。肿瘤坏死因子控制肿瘤生长速度的可能性存在 卵巢中的卵泡，防止这些结构的过度生长 变成了囊泡和肿瘤。然而，当卵巢中的肿瘤坏死因子供应耗尽时， 卵巢肿瘤的生长可能会增强。

DESCRIPTION (Adapted from the applicant's abstract): The goal of the studies proposed in this application is to elucidate the role of tumor necrosis factor (TNF) in follicular development and atresia in the rat. An antibody to human recombinant, TNF has been used to reveal the ovarian granulosa cell as a source of TNF. Human TNF has been found to stimulate follicular progesterone production in vitro. Studies proposed in this application will focus on whether TNF alters steroidogenesis of healthy and atretic follicles in an attempt to ascertain if TNF may be a trigger for the onset of follicular atresia. Using in vivo and in vitro experimental models of follicular atresia, I125-TNF binding to healthy and atretic follicles will be ascertained. Atresia will be prevented during sodium phenobarbital delayed ovulation in the rat with prolactin and the effects of TNF on follicular steroidogenesis in vitro and I125-TNF binding to follicles will be assessed. The effects of exogenous TNF in vivo on the morphology and steroidogenesis of healthy follicles will be determined. Several studies planned focus on whether the production of TNF can be hormonally regulated both in vivo and in vitro. Since TNF first appears during antrum formation, it is hypothesized that estrogen, FSH (and possibly LH) regulate its production. In addition, the effects of TNF on granulosal cell proliferation in vitro is of special interest. Since rat granulosal cells divide poorly in vitro, it is possible that this production of TNF is negatively modulating their growth. Therefore, granulosa cells will be grown in the presence of anti-TNF in order to determine whether their growth is enhanced. The discovery that TNF is present in the ovary of rat, cow and human indicates some universality of a role of TNF in its function. TNF has been shown experimentally to reduce tumor growth. The possibility exists that TNF controls the growth rate of follicles in the ovary and prevents excessive growth of these structures into cysts and tumors. However, when the ovarian TNF supply is exhausted, ovarian tumor growth may be enhanced.