Transcriptional repression of the glycoprotein hormone alpha subunit gene by androgen may involve direct binding of androgen receptor to the proximal promoter

Transcriptional Repression of the -Subunit Gene by Androgen Receptor Occurs Independently of DNA Binding but Requires the DNA-Binding and Ligand-Binding Domains of the Receptor

“…This study also identified a high-affinity binding site for androgen receptor (ARE) located between the tandem CREs and the CCAAT box in the proximal promoter region of the α-subunit gene (Fig. 1) (9). This site mapped to a previously identified promoter element, the junctional response element or JRE, which is important for expression in the placenta and has significant sequence identity to an ARE/glucocorticoid response element consensus site (9).…”

“…1) (9). This site mapped to a previously identified promoter element, the junctional response element or JRE, which is important for expression in the placenta and has significant sequence identity to an ARE/glucocorticoid response element consensus site (9). Based on these studies, we postulated that direct binding of activated AR to the JRE represses transcription of the α-subunit gene, accounting, at least partially, for the physiological regulation of the α-subunit by androgens.…”

“…Unlike negative regulation by glucocorticoid receptor, which predominantly exerts its negative regulatory effects by interacting with the transcription factor AP-1, the mechanism by which AR negatively influences transcription is less well understood. In one of the first reports on negative regulation by AR, we demonstrated that transcription of the α-subunit gene was repressed by androgens when promoter constructs, together with AR, were introduced into a gonadotrope cell line, αT3 (9). Repression was dependent on both the presence of AR and its ligand, dihydrotestosterone (DHT).…”

“…This gene is also regulated through feedback signals from the gonads (2,(4)(5)(6). Typically, estrogens and androgens synthesized in response to gonadotropin stimulation repress transcription of the αand gonadotropin β-subunit genes (4)(5)(6)(9)(10)(11)(12). Mechanistically, negative feedback by gonadal steroids may reflect either direct regulatory effects occurring at the level of the pituitary or an indirect mechanism involving inhibition of GnRH synthesis and secretion from hypothalamic neurons (4)(5)(6).…”

“…Mechanistically, negative feedback by gonadal steroids may reflect either direct regulatory effects occurring at the level of the pituitary or an indirect mechanism involving inhibition of GnRH synthesis and secretion from hypothalamic neurons (4)(5)(6). Several lines of evidence, however, suggest that direct transcriptional regulation of the α-subunit gene by androgens occurs within the pituitary and constitutes an important component of negative feedback (9,11,(13)(14)(15)(16).…”