LNCaP公司
二氢睾酮
醋酸环丙孕酮
雄激素受体
比卡鲁胺
部分激动剂
雄激素
化学
内分泌学
内科学
环丙孕酮
兴奋剂
生物
受体
生物化学
前列腺癌
激素
医学
癌症
作者
F. Chen,Kristin Knecht,Chih‐Tai Leu,Su Jane Rutledge,Angela Scafonas,Carlo J. Gambone,Robert L. Vogel,H. Zhang,Viera Kasparcova,Chang Bai,Satoru Harada,Azriel Schmidt,Alfred A. Reszka,Leonard P. Freedman
标识
DOI:10.1016/j.jsbmb.2004.04.009
摘要
Androgens play important endocrine roles in development and physiology. Here, we characterize activities of two “Andro” prohormones, androstenedione (A-dione) and 4-androsten-3β,17β-diol (A-diol) in MDA-MB-453 (MDA) and LNCaP cells. A-dione and A-diol, like cyproterone acetate, were partial agonists of transfected mouse mammary tumor virus (MMTV) and endogenous prostate-specific antigen (PSA) promoters. Different from bicalutamide but similar to CPA, both are inducers of LNCaP cell proliferation with only mild suppression of 5α-dihydrotestosterone (DHT)-enhanced cell growth. Like bicalutamide and cyproterone acetate, A-dione and A-diol significantly antagonized DHT/R1881-induced PSA expression by up to 30% in LNCaP cells. Meanwhile, in MDA cells, EC50s for the MMTV promoter were between 10 and 100 nM. Co-factor studies showed GRIP1 as most active for endogenous androgen receptor (AR), increasing MMTV transcription by up to five-fold, without substantially altering EC50s of DHT, A-dione or A-diol. Consistent with their transcriptional activities, A-dione and A-diol bound full-length endogenous AR from MDA or LNCaP cells with affinities of 30–70 nM, although binding to expressed ligand-binding domain (LBD) was >20-fold weaker. In contrast, DHT, R1881, and bicalutamide bound similarly to LBD or aporeceptor. Together, these data suggest that A-dione and A-diol are ligands for AR with partial agonist/antagonist activities in cell-based transcription assays. Binding affinities for both are most accurately assessed by AR aporeceptor complex. In addition to being testosterone precursors in vivo, either may impart its own transcriptional regulation of AR.
科研通智能强力驱动
Strongly Powered by AbleSci AI