B ERSON AND YALOW hardly ever worked directly on receptors, but they did make many key contributions that have led to the development of this area. It will be clear that scientists now working with peptide hormone receptors have appropriated directly methods and technical approaches that were devised by Berson and Yalow for radioimmunoassay. Further, Berson and Yalow helped create and formulate concepts and ideas-for example the unity of the peptide hormones-that have led to the swift spread of receptor studies from one hormone to another. In reading further, much of the debt to Berson and Yalow will be obvious, while their other contributions are more subtle but equally important. I shall try to highlight these in the last section of the paper. For a hormone to activate a target tissue, it must first bind to some constituent of the cell. This first step in polypeptide hormone action had been studied indirectly for many years by measuring some effect of the hormone, but it was not until 1969 that this key step was measured directly. In that year two groups. using ““I-ACTH and “‘1-angiotensin, respectively, demonstrated methods that were applicable generally for the direct study of the interaction of peptide hormones and their specific receptors on target cells.’’The approach has been extended by dozens of laboratories to many other peptide hormones (Table I), and an enormous amount of new direct information has been gathered about hormone-receptor interactions including the number of receptor sites per cell. their affinity and specificity, the speed of hormone binding and dissociation, measurements of hormone in plasma and demonstrations of alterations in receptors in association with disease states in animals and man.

EARLY DIRECT STUDIES The idea of using radioactively labeled peptide hormones to study directly peptide hormone-receptor interactions was not new in 1969, but two barriers had to be overcome that had thwarted earlier investigations. First, hormone had to be prepared at very high specific radioactivity that retained biologic activity. Isotopes of iodine are technically the easiest to use, but with regard to biologic activity of peptide hormones, they were treated with suspicion. Al-