This Program Project entitled, "Studies of Conadotropins" is composed of four research projects and two core facilities. Its central theme is to improve the understanding of gonadotropin structure-function relationships and to improve methods to quantify gonadotropins in studies of human reproduction. The first research project entitled, "Hormone Structure and Function" will be directed by Dr. William Moyle and applies the techniques of genetic engineering to make modifications in gonadotropin gene structure, so the expressed products can be evaluated for alterations of function. Alterations to be studied include hormone receptor binding and biological activity, and it is expected that the results will define the amino acids that contribute to the structure of antibody binding sites. The second research project entitled, "Protein Chemistry of Gonadotropins and Fragments" will be directed by Dr. Steven Birken and applies the techniques of protein chemistry to the genetically-altered proteins produced by Project I and also attempts to solve the location of the disulfide bridges in the native structure of Gonadotropin subunits, as well as the origins and structure of gonadotropin fragments that are employed as disease markers. Project III entitled, "Biophysical and Immunochemical Studies of Gonadotropins" will be directed by Dr. Canfield, and this will serve as the interface of all disciplines in the program with a special emphasis on protein physical chemistry and immunology. The goal is to increase understanding of the three-dimensional structure of gonadotropins by three-dimensional model building, NMR studies, protein crystallography experiments, and by producing novel antibodies to gonadotropins, whose defined epitopes provide useful information about the surface arrangement of amino acids. Project IV entitled, "Clinical Applications of Gonadotropin Measurement" will be directed by Dr. John O'Connor, and its goal is to apply immunologic techniques to improve clinical research measurements related to early pregnancy loss, ovulation, and other reproductive events. This program will also include an Administrative Core Facility, directed by Dr. Canfield, and a Tissue Culture and Hybridoma Core, directed by Dr. Alexander Krichevsky. Both will provide services to all four research projects.