Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens

The competition of a series of steroidal androgens and steroidal and non-steroidal antiandrogens, with [ 3H]-methyltrienolone, for androgen receptor binding sites of the rat prostate, has been studied under conditions designed to distinguish between agonists and antagonists. The antiandrogenic activity of these compounds was determined in both castrate and intact male rats. Androgenic activity was monitored by measurements of prostate growth in castrate rats and also by induction of prostatic S-adenosyl- l-methionine decarboxylase. We report for the first time the existence of partial agonist (androgenic) activity in a number of novel antiandrogens. In these studies no correlation was established between biological potency and relative receptor binding affinity. We were also unable to distinguish unequivocally between agonists and antagonists on the basis of receptor binding behaviour.