Endocrine-Immune Interactions: Estrogens as Immunomodulators

动物的内分泌系统使用激素来调节身体的几乎所有内部功能，而免疫系统则保护身体免受外部攻击。特别是类固醇激素，是生长和繁殖的重要调节剂，但有些类固醇激素，如睾酮，会抑制免疫功能。相反，雌激素通常刺激免疫功能。由于雌性经常将类固醇激素和免疫分子传递给后代，这些母体贡献可能会增强或削弱后代的免疫功能。该项目将使用产卵的红耳滑龟来测试这样一种假设，即在胚胎发育期间提高雌激素是雌性可以操纵其后代发育中的免疫系统的一种方式。由于雌龟产蛋后不提供父母照顾，它们只能通过向蛋黄提供雌激素和抗体等资源来操纵它们正在发育的后代。鸡蛋将暴露于（i）升高水平的雌激素（17 β-雌二醇），（ii）阻断雌激素产生的化学物质，或（iii）17 β-雌二醇和雌激素产生阻断剂的组合。据预测，如果雌激素增强免疫功能，则来自17 β-雌二醇处理的蛋的动物将具有比对照组和用雌激素阻断剂处理的蛋更高的免疫应答性。与对照组相比，雌激素治疗的成年雌海龟的免疫反应性有所改善的假设也将得到验证。这项研究将阐明雌激素暴露在早期发育和成年期的潜在影响。这些信息是必要的，因为许多环境污染物模拟雌激素的影响。只有通过实验操纵雌激素暴露，才能确定模拟雌激素的环境污染物对动物自然种群的影响。此外，该项目将为一些本科生和研究生提供实地和实验室方法的研究培训。

The endocrine system of animals uses hormones to regulate virtually every internal function of their bodies while the immune system defends the body against attack from the outside. Steroid hormones, in particular, are important regulators of growth and reproduction, but some steroid hormones, such as testosterone, depress immune function. In contrast, estrogens generally stimulate immune function. Because females often transfer steroid hormones and immune molecules to their offspring, immune function of offspring may be enhanced or impaired by these maternal contributions. This project will use the egg-laying red-eared slider turtle to test the hypothesis that elevating estrogens during embryonic development is a way that females can manipulate the developing immune system of their offspring. Because female turtles provide no post-laying parental care, they can only manipulate their developing offspring by providing resources, such as estrogens and antibodies, to the egg yolk. Eggs will be exposed to (i) elevated levels of estrogen (17ß-estradiol), (ii) to a chemical that blocks estrogen production, or (iii) to a combination of both 17ß-estradiol and the estrogen-production blocker. It is predicted that if estrogens enhance immune function, animals from 17ß-estradiol treated eggs will have higher immune responsiveness than controls and eggs treated with the estrogen blocker. The hypothesis that adult female turtles treated with estrogen will have improved immune responsiveness compared with controls will also be tested. This research will clarify the potential effects of estrogen exposure during both early development and in the adult. Such information is needed because many environmental contaminants mimic the effects of estrogens. Only by experimentally manipulating estrogen exposure can the effects of estrogen-mimicking environmental contaminants on natural populations of animals be identified. In addition, this project will provide research training to a number of undergraduate and graduate students in both field and laboratory-based methods..