Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity.
The androgen and glucocorticoid hormones elicit divergent and often opposing effects in cells, tissues, and animals. A wide range of physiological and molecular biological evidence suggests that the receptors that mediate these effects, the androgen and glucocorticoid receptors (AR and GR, respectively), influence each other's transcriptional activity. We now show that coexpressed AR and GR indeed do interact at the transcriptional level and that this interaction is correlated with their ability to form heterodimers at a common DNA site, in vitro and in vivo. Furthermore, mutants that cannot heterodimerize do not inhibit each other's activity. These observations provide the first evidence that the opposing physiological effects of the androgen and glucocorticoid hormones are due to the direct physical interaction between their receptors at the transcriptional level.
Chen
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Division of Nephrology, Department of Medicine, San Francisco General Hospital, and Biomedical Sciences Program, University of California, San Francisco, California 94143, USA.
Wang
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Yu
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Liu
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Pearce
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D000728:Androgens / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D019281:Dimerization; D005938:Glucocorticoids / Q000378:metabolism; D000882:Haplorhini; D009154:Mutation; D011940:Receptor Aggregation; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
D000728:Androgens; D005938:Glucocorticoids; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid