Regulation of Ecdysteroid Hormone Biosynthesis

9603547 Spaziani甲壳类动物断肢的生长、蜕皮和再生是由一对腺体（y型器官）分泌的类固醇激素（外体类固醇）控制的。反过来，y型器官是由动物大脑中的一种蛋白质激素（MIH）调节的。这个系统与分泌类固醇激素（睾酮、雌激素、可的松）的人体腺体（睾丸、卵巢、肾上腺）类似，这些激素由来自大脑和脑下垂体的蛋白质激素控制。PI发现甲壳类动物和人类一样，可以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，甲壳类动物的腺体被用作简化模型来研究胆固醇是如何进入细胞的，这些细胞是如何将其转化为激素的，以及这一过程是如何由大脑激素控制的。这个项目的重点是研究膨胀是如何从细胞表面转移到细胞内部的，细胞表面含有“识别”MIH和HDL的受体，最终转移到负责激素合成的酶的编码基因上。具体来说，这个假设将被验证，即信息信号是导致(a)膜酶激活和(b)细胞内钙释放的特殊脂质，两者反过来负责激活激素合成途径中的关键酶。一些问题集中在激素合成的增加是否可能由循环中的钙的增加以及细胞中已经存在的钙的增加引起。方法包括使用放射性钙作为示踪剂和荧光指示剂检测细胞内钙的释放。研究结果将有助于解开脊椎动物腺体的相关谜团。总的来说，这项研究有助于了解甲壳类动物及其昆虫近亲的生物学，以及经济上重要的动物类群，并涵盖神经生物学，内分泌学和发育学领域，解决神经内分泌协调和类固醇激素分泌控制的基本问题。＊＊＊

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. ***