This proposal seeks to continue investigations into the design and synthesis of halogenated analogs of steroid hormones. Synthetic procedures will be developed which will permit the incorporation of radioactive iodine (125I and 123I) and fluorine (18F) into androgens and glucocorticoids which will subsequently retain their hormonal activity. Radiolabeled androgens will be useful for the sensitive detection of androgen responsive tumors such as prostate cancer and for quantifying the androgen receptor in vitro. They will also have great utility for autoradiographic studies of tissues, such as brain, in which the androgen receptor is present, but localized in specific cells or regions. Such studies have great value in elucidating the role of androgens in processes such as the sexual differentiation of the brain in fetal development. Labeled compounds with glucocorticoid activity will be valuable in mapping and imaging of glucocorticoid receptor rich regions of the brain. Since the specific neurophysiological mechanisms by which corticosteroids influence neuronal function are not fully understood, such studies are of increasing importance in defining and understanding their role and function in the brain. In earlier work this laboratory has successfully emphasized the development of radiolabeled progestins and androgens with later interest developing in glucocorticoids. This proposal represents the next evolutionary step in our work, which will complete our studies of androgens and more heavily emphasize the development of high affinity ligands for the glucocorticoid receptor. Several potential iodinated or fluorinated ligands for this androgen and glucocorticoid receptors will be synthesized and then tested in this collaborative study for their ability to compete for binding to the entire array of steroid receptors. The same precursors of these non-radioactive halogenated steroid analogs will be used to synthesize the radio-halogenated versions of these analogs which show favorable finding characteristics. These radioactive steroids will be studied in a battery of in vitro and in vivo hormonal assays to ascertain their ability to concentrate in tissues in a receptor mediated fashion. This proposal specifically requests funding for the chemical synthesis of the non-radioactive ligands and their precursors.