TRANSCRIPTIONAL REPRESSION OF THE ALPHA-SUBUNIT GENE BY ANDROGEN RECEPTOR OCCURS INDEPENDENTLY OF DNA-BINDING BUT REQUIRES THE DNA-BINDING AND LIGAND-BINDING DOMAINS OF THE RECEPTOR

The pituitary glycoprotein hormones LH and FSH regulate the reproducti ve cycle and are sensitive to feedback by gonadal steroids. The common alpha-subunit shared by these hormones is transcriptionally repressed by androgen receptor (AR) in the presence of its ligand dihydrotestos terone. This identifies at least one mechanism that contributes to AR- dependent suppression of gonadotropin synthesis, Repression of alpha-s ubunit transcription by AR requires only the sequences within the firs t 480 bp of the promoter, While this region contains a high-affinity b inding site for AR, this element does not mediate the suppressive effe cts of androgens, Instead, two other elements within the promoter-regu latory region (alpha-basal element and cAMP-regulatory element), which are important for expression of the alpha-subunit gene in gonadotrope s, mediate the effects of AR. This suggests that AR inhibits activity of the alpha-subunit promoter by interfering with the transcriptional properties of the proteins that bind to alpha-basal element and the cA MP-regulatory elements. Furthermore, transfection analysis of various mutant ARs identified both the DNA-binding and ligand-binding domains of the receptor as critical for repression, Comparisons with the MMTV promoter revealed distinct structural requirements that underlie the t ransactivation and transrepression properties of AR.