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 reproductive 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 dihydrotestosterone. This identifies at least one mechanism that contributes to AR-dependent suppression of gonadotropin synthesis. Repression of alpha-subunit transcription by AR requires only the sequences within the first 480 bp of the promoter. While this region contains a high-affinity binding site for AR, this element does not mediate the suppressive effects of androgens. Instead, two other elements within the promoter-regulatory region (alpha-basal element and cAMP-regulatory element), which are important for expression of the alpha-subunit gene in gonadotropes, 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 cAMP-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 transactivation and transrepression properties of AR.
Heckert
L L
LL
Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City 66160, USA.
Wilson
E M
EM
Nilson
J H
JH
D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010902:Pituitary Gland / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D008024:Ligands; D011944:Receptors, Androgen; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA