title: Intracellular inactivation, reactivation and dynamic status of prostate androgen receptors.
abstract: The dynamic status of the androgen receptor in prostate cells was studied by incubation of rat ventral prostate with radioactive 17beta-hydroxy-5alpha-androstan-3-one (5alpha-dihydrotestosterone) in the presence and absence of respiratory poisons and inhibitors of protein and RNA synthesis and also by isotope chasing of the radioactive androgen-receptor complexes. The androgen receptor in the prostate appears to go through a dynamic process of recycling between the cytoplasm and the nucleus as well as an inactivation process. The radioactive androgen-receptor complex, however, is maintained at a constant level for at least 2h during incubation at 37 degrees C, even in the absence of new protein synthesis, suggesting that early androgen actions may not require a depletion of a major portion of cellular receptor. In the presence of 2,4-dinitrophenol, the androgen receptor is rapidly deactivated (half life, 2min). The inactive receptor can be reactivated efficiently by an energy-dependent process, even in the absence of protein synthesis. Receptor binding of androgen and nuclear chromatin binding of the androgen-receptor complex are fast processes; half-maximum binding can be achieved within 1 and 10min respectively. On the contrary, the overall process of the release of the receptor complex from nuclear chromatin and its reappearance in the cytosol fraction has a long half life of about 70min. This slow process may reflect the involvement of the steroid-receptor complex in a time-consuming mechanism that is essential for hormone responses. Actinomycin D can increase the nuclear receptor level by 50% or more. This increase is not due to a decrease in the rate of receptor release from nuclei or to inhibition of DNA degradation by the antibiotic.
mesh_terms: D019297:2,4-Dinitrophenol; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011467:Prostate / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004140:Dinitrophenols; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D014475:Uncoupling Agents; D013196:Dihydrotestosterone; D003609:Dactinomycin; D003513:Cycloheximide; D019297:2,4-Dinitrophenol