Mechanistic insights into steroid hormone-mediated regulation of the androgen receptor gene

Author:

Gillen Andrew D.ORCID,Hunter Irene,Ullner EkkehardORCID,McEwan Iain J.ORCID

Abstract

Expression of the androgen receptor is key to the response of cells and tissues to androgenic steroids, such as testosterone or dihydrotestosterone, as well as impacting the benefit of hormone-dependent therapies for endocrine diseases and hormone-dependent cancers. However, the mechanisms controlling androgen receptor expression are not fully understood, limiting our ability to effectively promote or inhibit androgenic signalling therapeutically. An autoregulatory loop has been described in which androgen receptor may repress its own expression in the presence of hormone, although the molecular mechanisms are not fully understood. In this work, we elucidate the mechanisms of autoregulation and demonstrate, for the first time, that a similar repression of the AR gene is facilitated by the progesterone receptor. We show that the progesterone receptor, like the androgen receptor binds to response elements within the AR gene to effect transcriptional repression in response to hormone treatment. Mechanistically, this repression involves hormone-dependent histone deacetylation within the AR 5’UTR region and looping between sequences in intron 2 and the transcription start site (TSS). This novel pathway controlling AR expression in response to hormone stimulation may have important implications for understanding cell or tissue selective receptor signalling.

Funder

Friends of ANCHOR

NHS Grampian

Publisher

Public Library of Science (PLoS)

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3