Sex steroids and the thymus

性类固醇和胸腺

• 批准号: 6868248
• 负责人: GILBERT J. KERSH
• 金额: $ 7.65万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868248
• 关键词: T cell receptor; apoptosis; cell growth regulation; estrogens; hormone regulation /control mechanism; laboratory mouse; molecular cloning; morphology; pregnancy; progesterone; receptor binding; sex hormones; steroid hormone; thymus

DESCRIPTION (provided by applicant): A relationship exists between the gonads and the thymus. Castration results in a significant increase in the size of the thymus, and elevated serum levels of sex hormones results in a significant decrease in the size of the thymus. This is most evident during pregnancy where serum levels of progesterone and estrogen are very high, and the thymus shrinks to only 10% of its original size. There is also some evidence that the thymus can regulate the gonads. Thymectomized animals and animals congenitally athymic have been reported to have problems with reproduction and gonad function. This is presumably due to limited production of hormones by the thymus. Two lines of thought have developed to explain the thymus-gonad relationship. The most prominent idea is that it must be important to shrink the thymus during pregnancy. This could either be because of a need to limit the production of new T cells, or to limit the production of thymic hormones. The second line of thought is that the thymus and gonads in normal situations regulate each others function as a means to maintain homeostasis. In this case, pregnancy is an exceptional situation where thymic regulation of sex hormones is overcome by other mechanisms. In non-pregnant animals, the thymus limits the production of sex hormones by the gonads, and sex hormones limit the size and function of the thymus so that an optimum output is maintained for both organs. In this proposal, we outline experiments that will test both of these ideas. We propose to: 1) determine the cellular targets for estrogen and progesterone that lead to thymic involution; 2) determine whether the thymus-dependent hormone thymulin can increase levels of estrogen and/or progesterone; and 3) test whether production of new T cells, or production of thymulin, is detrimental to pregnancy.

描述（由申请人提供）：性腺与胸腺之间存在关系。 cast割导致胸腺的大小显着增加，性激素的血清水平升高会显着减少胸腺的大小。这在怀孕期间最明显的是，血清孕酮和雌激素水平很高，胸腺仅收缩至原始大小的10％。还有一些证据表明胸腺可以调节性腺。据报道，胸膜切除的动物和动物在无胸腺症中存在繁殖和性腺功能的问题。这大概是由于胸腺对激素的产生有限。已经发展了两种思路来解释胸腺的关系。最突出的想法是，在怀孕期间缩小胸腺必须很重要。这可能是因为需要限制新的T细胞的产生，或者限制胸腺激素的产生。第二道的思想是，正常情况下的胸腺和性腺可以作为维持体内平衡的手段。在这种情况下，怀孕是一种特殊情况，在其他机制中克服了性激素的胸腺调节。在非怀孕的动物中，胸腺限制了性腺的产生性激素，性激素限制了胸腺的大小和功能，从而使两个器官保持最佳输出。在此提案中，我们概述了将测试这两个想法的实验。我们提出：1）确定导致胸腺不足的雌激素和孕激素的细胞靶标； 2）确定胸腺依赖性激素胸腺素是否可以增加雌激素和/或孕酮的水平； 3）测试新T细胞的产生或胸腺素的产生是否不利于妊娠。