Regulation and Biosynthesis of Ecdysteroid Hormones

蜕皮类固醇激素的调节和生物合成

• 批准号: 9221790
• 负责人: Eugene Spaziani
• 金额: $ 22.8万
• 依托单位: University of Iowa
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-03-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9221790&HistoricalAwards=false
• 关键词: Regulation; Biosynthesis; Ecdysteroid; Hormones

Growth, molting and regeneration in crustaceans is controlled by steroid hormones (ecdysteroids) from a pair of glands (Y-organs) in the body cavity. The Y-organs in turn are regulated by a protein hormone (MIH) from the brain. This system is comparable to human glands (testis, ovary, adrenal) that secrete steroid hormones (testosterone, estrogen, cortisone) and are controlled by protein hormones from pituitary and brain. We have found that crustaceans, like humans, make steroid hormones from cholesterol. Accordingly, we use crustacean glands as a simplified model to study how cholesterol enters cells and is converted to hormones, and how the process is regulated by the external proteins. We already know that all cholesterol in crustacean blood is bound to high-density lipoprotein (HDL), and that there are receptors on the surface of Y-organ that recognize and bind the HDL. Using radioactively labeled cholesterol and HDL, the electron microscope and the ultracentrifuge, we now will find how cholesterol enters the cells, how it is processed if still bound to HDL and where in the cells the processing takes place. Part of the study is to determine how MIH controls cholesterol entry; e.g., does MIH change the number of receptors for HDL? We will also attempt to work out the details of the biosynthesis of ecdysteroids, by using the mass spectrograph to identify the individual steps in the conversion of cholesterol to the hormones. This project embraces the fields of neurobiology, endocrinology and development in addressing basic questions on neuroendocrine coordination of functions.

甲壳类动物的生长、蜕皮和再生是由 来自一对腺体（Y器官）的类固醇激素（蜕皮激素） 体腔。Y器官反过来又受一种蛋白质的调节 激素（MIH）从大脑。这个系统可以和人类的 分泌类固醇激素的腺体（睾丸、卵巢、肾上腺） （睾酮，雌激素，可的松），并由蛋白质控制 垂体和大脑分泌的激素。我们发现甲壳类动物， 像人类一样，从胆固醇中制造类固醇激素。因此，委员会认为， 我们用甲壳类动物的腺体作为一个简化的模型来研究 胆固醇进入细胞并转化为激素， 这一过程受外部蛋白质的调控。我们已经知道 甲壳类动物血液中的胆固醇 脂蛋白（HDL），并有受体的表面上， 识别和结合HDL的Y-器官。使用放射性 标记的胆固醇和HDL，电子显微镜和 我们现在将发现胆固醇是如何进入细胞的， 如果它仍然与HDL结合，它是如何加工的，以及在细胞中的位置， 进行处理。这项研究的一部分是为了确定 MIH控制胆固醇进入;例如，MIH是否会更改 HDL受体我们亦会尝试研究 蜕皮甾体的生物合成，通过使用质谱仪， 确定胆固醇转化为 荷尔蒙这个项目涵盖了神经生物学， 内分泌学与发展在解决 神经内分泌功能的协调。