Regulation of Ecdysteroid Hormone Biosynthesis

蜕皮类固醇激素生物合成的调节

• 批准号: 9603547
• 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: 1997
• 资助国家: 美国
• 起止时间: 1997-02-15 至 2001-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9603547&HistoricalAwards=false
• 关键词: Regulation; Ecdysteroid; Hormone; Biosynthesis

9603547 Spaziani Growth, molting and regeneration of lost limbs in crustaceans is controlled by steroid hormones (ecdysteroids) from a pair of glands (Y-organs). The Y-organs, in turn, are regulated by a protein hormone (MIH) from the animals' brain. This system is comparable to human glands (testes, ovaries, adrenals) that secrete steroid hormones (testosterone, estrogen, cortisone) and that are controlled by protein hormones from the brain and pituitary gland. The PI has found that crustaceans, like humans, make steroid hormones from cholesterol and that the cholesterol in blood is bound up in lipoprotein (HDL). Accordingly, crustacean glands are being used as a simplified model to study how cholesterol enters cells, how those cells converted it to hormones, and how the process is controlled by the brain hormone. The project focuses on how inflation is transferred from the cell surface, which contains receptors that "recognize" MIH and HDL, to the interior, ultimately to genes that code for enzymes responsible for hormone synthesis. In particular, the hypothesis will be tested that informational signals are specialized lipids which cause (a) the activation of membrane enzymes, and (b) the release of intracellular calcium, both in turn responsible for activation of key enzymes in the path toward hormone synthesis. A subset of questions centers on the probability that increased hormone synthesis can be triggered by rises of calcium in the circulation as well as by calcium already resident in the cell. Methods include use of radioactive calcium as tracer and fluorescence indicators that detect release of intracellular calcium. The research results will help to solve related mysteries in vertebrate glands. Generally, this research contributes to knowledge of the biology of crustaceans and their insect relatives, economically important animal groups, and embraces the fields of neurobiology, endocrinology and development in addressing basic questions on neuroendocrine coordination and control of steroid hormone secretion. ***

小行星9603547 甲壳类动物的生长、蜕皮和断肢的再生是由一对腺体（Y器官）中的类固醇激素（蜕皮激素）控制的。 而Y器官则由动物大脑中的一种蛋白质激素（MIH）调节。 该系统与人类腺体（睾丸、卵巢、肾上腺）相当，人类腺体分泌类固醇激素（睾酮、雌激素、可的松），并由大脑和脑垂体的蛋白质激素控制。 PI发现甲壳类动物和人类一样，从胆固醇中产生类固醇激素，血液中的胆固醇与脂蛋白（HDL）结合在一起。 因此，甲壳类腺体被用作研究胆固醇如何进入细胞的简化模型，这些细胞如何将其转化为激素，以及该过程如何由大脑激素控制。 该项目的重点是通货膨胀是如何从细胞表面转移到内部的，细胞表面含有“识别”MIH和HDL的受体，最终转移到编码负责激素合成的酶的基因。 特别是，将测试的假设，即信息信号是专门的脂质，导致（a）膜酶的激活，和（B）细胞内钙的释放，这两个反过来又负责激活的关键酶的路径激素合成。 一个问题的子集集中在增加激素合成的可能性，可以通过循环中钙的上升以及已经驻留在细胞中的钙来触发。 方法包括使用放射性钙作为示踪剂和检测细胞内钙释放的荧光指示剂。 研究结果将有助于解决脊椎动物腺体中的相关谜团。 一般来说，这项研究有助于了解甲壳类动物及其昆虫亲属，经济上重要的动物群体的生物学，并涵盖神经生物学，内分泌学和发展领域，解决神经内分泌协调和类固醇激素分泌控制的基本问题。 ***