From estrogen to androgen receptor: a new pathway for sex hormones in prostate.
While all three coactivators ARA70, steroid receptor coactivator 1, and RAC3/ACTR can enhance androgen receptor (AR) transcriptional activity at 1 nM dihydrotestosterone, we here demonstrate that only ARA70 can induce AR transcriptional activity >30-fold in the presence of 10 nM 17beta-estradiol (E2), but not diethylstilbestrol. The significance of this newly described E2-induced AR transcriptional activity in DU145 human prostate cancer cells was further strengthened by finding patients with Reifenstein partial-androgen-insensitive syndrome that fail in the E2-AR-ARA70 pathway. Together, our data suggest, for the first time, testosterone/dihydrotestosterone may not be the only ligands for the AR. E2 represents another important natural ligand for AR that may play an essential role for the AR function and the development of the male reproductive system.
Yeh
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S
George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Biochemistry, University of Rochester, Rochester, NY 14642, USA.
Miyamoto
H
H
Shima
H
H
Chang
C
C
D000595:Amino Acid Sequence; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D051548:Histone Acetyltransferases; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D011467:Prostate / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism; D011944:Receptors, Androgen / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D012739:Gonadal Steroid Hormones; C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D004958:Estradiol; D004054:Diethylstilbestrol; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3