Modulation of Androgen Receptor Transcriptional Activity by the Estrogen Receptor

Abstract

ABSTRACT: Estrogen/androgen receptor interactions in naturally occurring physiological 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 hormone receptors we have examined the effect of cotransfection of androgen (AR) and estrogen receptor (ER) cDNAs on the expression of the mouse mammary tumor virus long terminal repeat region (MMTV‐LTR) linked to the chloramphenicol‐acetyl‐transferase (CAT) reporter gene. In QT6 cells, which contain neither AR nor ER, cotransfection of AR cDNA with the MMTV‐LTR‐CAT reporter, resulted in transactivation only in the presence of dihydrotestosterone (DHT). Treatment with 10−8 M each of estradiol‐17β (E2), dexamethasone, or progesterone did not enhance CAT activity, whereas treatment with the androgens DHT and mibolerone resulted in 87% and 89% CAT activity. Transfection of increasing concentrations of ER cDNA in the presence of 100 ng of AR cDNA and 10−8 M each of DHT and E2 showed a dose‐dependent decrease in CAT activity as compared to the response with DHT alone. Cotransfection of AR and ER cDNA in the presence of 10−8 M DHT and increasing concentrations of E2 resulted in a dose‐dependent decrease in CAT activity. When cells were treated with increasing concentrations of DHT with 10−8 M E2 no significant increase in CAT activity was observed. In GC cells, which contain endogenous ER but no AR, cotransfection of AR cDNA and treatment with E2 and DHT, also reduced DHT‐induced CAT activity. Thus, we conclude that the E2 ER complex is capable of inhibiting transcriptional activity of the AR.