MODULATION OF ANDROGEN RECEPTOR TRANSCRIPTIONAL ACTIVITY BY THE ESTROGEN-RECEPTOR

Estrogen/androgen receptor interactions in naturally occurring physiol ogical systems and the effect of their respective steroid hormones on transcriptional activity remain undefined. In an attempt to delineate further the nature of the interaction between these two steroid hormon e receptors we have examined the effect of cotransfection of androgen (AR) and estrogen receptor (ER) cDNAs on the expression of the mouse m ammary tumor virus long terminal repeat region (MMTV-LTR) linked to th e chloramphenicol-acetyltransferase (CAT) reporter gene. In QT6 cells, which contain neither AR nor ER, cotransfection of AR cDNA with the M MN-LTR-CAT reporter, resulted in transactivation only in the presence of dihydrotestosterone (DHT). Treatment with 10(-8) M each of estradio l-17 beta (E(2)), dexamethasone, or progesterone did not enhance CAT a ctivity, whereas treatment with the androgens DHT and mibolerone resul ted in 87% and 89% CAT activity. Transfection of increasing concentrat ions of ER cDNA in the presence of 100 ng of AR cDNA and 10(-8) M each of DHT and E(2) showed a dose-dependent decrease in CAI activity as c ompared to the response with DHT alone. Cotransfection of AR and ER cD NA in the presence of 10(-8) M DHT and increasing concentrations of E( 2) resulted in a dose-dependent decrease in CAT activity. When cells w ere treated with increasing concentrations of DHT with 10(-8) M E(2) n o significant increase in CAT activity was observed. In GC cells, whic h contain endogenous ER but no AR, cotransfection of AR cDNA and treat ment with E(2) and DHT, also reduced DHT-induced CAT activity. Thus, w e conclude that the E(2)/ER complex is capable of inhibiting transcrip tional activity of the AR.