Differential regulation of testosterone vs. 5 alpha-dihydrotestosterone byselective androgen response elements

There are two major physiological androgens, testosterone (T), and 5 alpha- dihydrotestosterone (DHT), which induce different responses in mammals. The se androgens regulate the target gene transcription via binding to and acti vating the same androgen receptor (AR). The molecular mechanisms that diffe r between these two very close androgens through the same AR protein to tar get the distinct genomic responses remain unknown. Using yeast genetic sele ction, we identified two kinds of androgen response elements (ARE), which c ould respond differentially to T vs. DHT. These two AREs also show differen t T-vs. DHT-induced AR transactivation in mammalian Chinese hamster ovary ( CHO) cells in terms of copy number and comparisons with the classic mouse m ammary tumor virus ARE. Together, our results suggest that the selective AR E sequence may play an important role in the differential T- vs. DHT-induce d AR transactivation.