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The estrogen receptor-related receptor alpha (ERRalpha) is an orphan member of the nuclear receptor superfamily that has been shown to interfere with the estrogen-signaling pathway. In this report, we demonstrate that ERRalpha also cross-talks with signaling driven by other steroid hormones. Treatment of human prostatic cells with a specific ERRalpha inverse agonist reduces the expression of several androgen-responsive genes, in a manner that does not involve perturbation of androgen receptor expression or activity. Furthermore, ERRalpha activates the expression of androgen response elements (ARE)-containing promoters, such as that of the prostate cancer marker PSA, in an ARE-dependent manner. In addition, promoters containing a steroid response element can be activated by all members of the ERR orphan receptor subfamily, and this, even in the presence of antisteroid compounds.

The orphan receptor ERRα interferes with steroid signaling