Reverse endocrinology as an approach to drug discovery

This manuscript is intended to provide a summary of a relatively new approach to drug discovery that has been termed 'reverse endocrinology'. Traditionally, hormones were identified on the basis of their physiological effects, i.e., they were purified, characterized chemically and their physiological effects determined. Identification of their specific receptor(s) followed through ligand-receptor interaction studies utilizing radioactive ligands. Finally, the gene and its chromosomal location were characterized. In reverse endocrinology, molecular biological approaches permit the identification of orphan receptors first and, subsequently, their specific ligands. In this manner, new synthetic ligands can be tested in reporter gene activation assays to eventually open up possibilities and suggest selective ligands as new drugs in endocrine and related diseases.