The proposed studies are designed to examine the interaction of agonists and antagonists with the estrogen receptor and their ability to activate the receptor to the DNA binding state using newly advised equilibrium methods. A new hypothesis for the mechanism of androgen antagonism of estrogen action will be tested both in vitro and in vivo. Additionally, studies of the apparent resistance to steroid hormones observed in New World primates will be carried out. Characterization of plasma and tissue steroid levels as well as binding to transport proteins and receptors will be performed. The possibility that the elevated levels of steroids are the consequence of defects in enzymes that metabolize steroids rather than receptors will be tested by several approaches. This will include comparison of steroid levels in plasma and body fluids such as saliva, studies of steroid metabolism by tissues, and study of steroid dynamics in vivo. The effects of massive aromatization of androgens to estrogens occurring in the male squirrel monkey will be determined. In particular, the influence of the resulting large amounts of estrogens, together with androgens on events such as pubertal development and seasonal weight changes, will be explored. (Y)
