Interactions between androgen and estrogen receptors and the effects on their transactivational properties

The physiological interplay of androgen and estrogen action in endocrine tissues is well recognized. The biochemical processes responsible for this interplay have yet to be fully defined. We have demonstrated that the androgen receptor (AR) and estrogen receptor-alpha (ER alpha) can interact directly using the yeast and mammalian two-hybrid systems. These interactions occurred between the C-terminal ER alpha ligand-binding domain and either the N-terminal AR transactivational domain or the full-length AR. Estrogen receptor-beta (ER beta) did not interact with the AIR. DNA cotransfection studies employing AR, ER alpha and ER beta expression vectors and AR- or ER-reporter gene constructs were used to identify and measure potential functional effects of AR-ER interaction. Coexpression of ER alpha with AR decreased AK transactivation by 35%; coexpression of AR with ER alpha decreased ER alpha transactivation by 74%. Coexpression of AR and ER beta did not significantly modulate AR or ER beta transactivation. In summary, we have shown that specific domains of AR and ER alpha physically interact and have demonstrated the functional consequences of such interaction. These results may help explain the nature of the physiological interplay between androgens and estrogens. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.