Formation of Ecdysteroid Hormones in Crustaceans

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Two hormones control the cycles of growth, molting and regeneration in arthropod animals (insects and crustaceans). In crustaceans, one of the hormones is ecdycsone, chemically a steroid, that directly controls the cycles. Ecdysone is secreted by glands (Y-organs) in the body cavity. Secretion by the Y-organs is controlled in turn by the second hormone, molt-inhibiting hormone (MIH) which is chemically a protein and is secreted by specialized nerve cells in the brain. This system is analogous to that in the human and other vertebrates (adrenal cortex, ovary and testis) that secrete steroid hormones and that are governed by protein hormones from the brain/pituitary gland. However, the crustacean system is simpler in cell structure and metabolism. For this reason, the system is being used as a model for studying the details of how cells take up cholesterol (the universal precursor of steroid hormones) and process it for hormone synthesis, and how neural hormones control these events. The focus of this project is to uncover the mechanism by which cholesterol enters Y-organ cells in light of findings that cholesterol is presented to the cells bound up in high- density lipo-protein (HDL). Specific receptors for HDL on the cell surface, how the complex is broken down in the cell and how and where the freed cholesterol is processed into hormone will be examined. Attendant studies will explore how MIH modifies cell function to slow or stop hormone biosynthesis. In this regard, crustaceans appear to be unique among animals; a theoretically significant aspect of this model is that the brain hormone (MIH) regulates negatively, whereas in all other known systems the corresponding hormone is stimulatory. Techniques will include use of radioactive tracers, the electron microscope, the ultracentrifuge and high-pressure liquid chromatography. This research embraces the fields of neurobiology, endocrinology and developmental biology in addressing basic questions on coordination of bodily functions. Results should have eventual application of clinical medicine in the areas of steroid endocrinology, reproductive physiology, pathologies of glands and atherosclerosis (arising from defects in cholesterol metabolism). Also, knowledge gained will add to understanding the arthropod molting/growth cycle, a developmental process that dominates the existance of this abundant, economically important group of animals.