PROTEIN CHEMICAL STUDIES OF THE FORMS OF HCG

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The goals of this project are to apply protein chemistry to enhance our understanding of the nature of the crystallized form of hCG, to produce a properly folded hCG receptor fragment for three dimensional studies, and to determine the structures in serum and urine of hCG metabolites useful for diagnosis of diseases of reproduction. Hormone metabolic products have been shown to vary in pathological states and we intend to define the structures of such metabolites to improve their measurement and the understanding of their relationship to normal and abnormal physiology. This project combines our chemical capabilities to purify and structurally analyze minute quantities of proteins with our ability to develop and apply assays for measurement of these proteins. One major theme of this program is the collaborative studies with Projects II and III in an effort to produce properly-folded extracellular CG receptors for studies of the structure of the hormone-receptor interface. A second major theme is to determine the structures of hCG and hLH metabolites as markers of normal pregnancy, diseases of pregnancy and menopause. A third is to develop a nonhuman primate model of early pregnancy loss, EPL (loss of a chemically-detected pregnancy without any clinical evidence of pregnancy). The latter problem, resulting in a decline in human fertility, is a major social concern since it can result from exposure to environmental toxins. Our specific aims are to: (1) Perform Protein Chemical Studies Related to the Three-Dimensional Structures of the Gonadotropins and Their Receptors; (2) Isolate and determine the structures of forms of hCG and hLH from normal pregnant women, women with ectopic pregnancies, women undergoing ovulation induction and postmenopausal women; and (3) Develop and employ a primate model for the study of reproductive toxicology.