ANDROGEN RECEPTOR PROTEIN BINDING PROPERTIES AND TISSUE DISTRIBUTION OF 2-SELENA-A-NOR- 5a-ANDROSTAN-17S-OL IN THE RAT

ANDROGEN RECEPTOR PROTEIN BINDING PROPERTIES AND TISSUE DISTRIBUTION OF 2-SELENA-A-NOR5a-ANDROSTAN-17S-OL IN THE RAT. R. W. Scot Skinner, Rodney V. Pozderac, Raymond E. Counsell, Chen-Fu Hsu, and Paul A. Weinhold. Nuclear Medicine Service and the Biochemical Research Service (7169:02), Veterans Administration Hospital and the Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan. Received: S-21-77 ABSTRACT 2-selena-A-nor-5a-androstan-17p-ol was studied in vitro and -in vivo in the rat prostate gland. The data demonstrates the ability -of this compound to selectively complex with the specific receptors of 5a-dihydrotestosterone (5a-DHT) in the cytosol and to be retained in the nuclei in an unaltered form. Studies with selenium75 labeled material suggests that the uptake and localization is similar to endogenous 5a-dihydrotestosterone. INTRODUCTION Studies with rat prostate minces incubated in vitro have shown -that certain structurally modified steroids can inhibit the specific binding of ~Q-DHT-~H to androgen receptor protein (1, 2). These studies have emphasized the importance of the 17P-hydroxyl and planarity of the steroid nucleus for maximum binding affinity. In addition, in vivo studies have shown 17P-hydroxyandrostanea lacking -the C-3 oxygen retain significant androgenic activity. For example, 5a-androst-2-en-17p-ol (I) was found to have 50 percent of the androgenie activity of testosterone when compared after subcutaneous administration to rats (3). Moreover, the sulfur and selenium