Active Forms and Biodynamics of the Androgen-Receptor in Various Target Tissues

Abstract

Studies during the last several years have indicated that androgen action in the rat ventral prostate is dependent on the formation of a specific 5α-dihydrotestosterone-receptor complex, while in some target tissues, testosterone rather than 5α-dihydro-testosterone appears to bind the functional receptors. In tissues with receptors that have similar affinities toward the two androgens, the relative availability and the differential metabolic activity of the androgenic steroids may be the major factors determining which form plays the predominant role in the androgenic responses. In some target cells, androgens other than testosterone or 5α-di-hydrotestosterone may have their own specific receptors for their biological actions. The androgen insensitivity in various tissues of animals at old age or with testicular feminization and the in-sensitivity found in autonomous tumors, may be explained by low receptor content; in some cases, however, the qualitative and not the quantitative changes in the active forms of the androgen-recep-tor complexes may be responsible. Various androgens appear to bind to receptor proteins as if they are being “enveloped” by the latter. Such an interaction appears to cause the transformation of the receptor protein to the form that may be capable of functioning at the target site. There is no conclusive evidence, aside from the gross geometric structure, that any specific functional group or electronic structure is absolutely required for receptor binding and androgen action in the target cell.