Our objective is to conduct experiments for which the central theme is a study of the hormone, human chorionic gonadotropin (hCG). The overall goal of the program is to increase knowledge of the chemistry of this hormone, to stimulate new initiatives toward a determination of its tertiary structure, to improve upon the capability to detect hCG in biological specimens and to apply these improvements in clinical situations. In more specific terms, experiments to alter the surface characteristics of hCG will be conducted in an effort to determine what portion of the surface of the hormone is involved in biological recognition and to be able to characterize the location of specific antibody binding sites on the hormone. A collection of monoclonal antibodies to various regions of the hormone will be studied in an attempt to better define the precise location of their binding sites to this molecule. Peptide fragments containing portions of the sequence of the hormone will be synthesized for the purpose of generating additional antisera that are specific for the amino acid sequences of these defined regions on the surface of the molecule. A series of collaborative studies are proposed to measure distances between reference points at the surface of the hormone or its subunits when it is undergoing certain conformational changes. Another element of research consists of an effort to express the genes for the Alpha and Beta subunits of hCG both in bacterial and mammalian systems toward the goal of producing sufficient quantities of these polypeptide chains, free of carbohydrate, to crystallize for x-ray diffraction studies. An additional segment of research includes the development of improved and new immunoassays for the detection of hLH and of hCG, as well as its subunits and its carbohydrate altered forms, in urine specimens. These assays will be used in clinical investigations of normal fertile women and those undergoing donor insemination to determine the pattern of hCG excretion in early pregnancy. These assays will also be employed to measure rates of early fetal loss as well as to determine the pattern of hCG excretion in women wearing different types of IUDs. Finally, these new and more sensitive assays for hCG will be applied to study the detection and monitoring of the therapy of tumors of reproductive organs.
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