If as discussed below one subscribes to the idea that both T and DHT mediate their effects by interacting with a single nuclear receptor protein, then how can we account for the requirement of both T and DHT for sexual development? The answer may be found by examining the ability of these androgens to interact with the AR. Several investigators have demonstrated that T has approximately 3 times faster association and dissociation rates than DHT on both the rat (72) and human (73, 74) AR. In agreement with these binding kinetics, Zhou et al. have demonstrated that T is less effective at stabilizing AR than DHT (74). These observations suggest that DHT, by enhancing the stabilization of AR and its action, amplifies the T signal in those tissues which contain 5a-reductase. Perhaps in these tissues, the AR expression is not sufficient for T to mediate a physiologic response, but due to the ability of DHT to enhance AR activity, a response is observed.
