Abstract
Selective androgen receptor modulators (SARMs) specifically bind to the androgen receptor and exert agonistic or antagonistic effects on target organs. In this study, we investigated the SARM activity of TSAA-291, previously known as a steroidal antiandrogen, in mice because TSAA-291 was found to possess partial androgen receptor agonist activity in reporter assays. In addition, to clarify the mechanism underlying its tissue selectivity, we performed comprehensive cofactor recruitment analysis of androgen receptor using TSAA-291 and dihydrotestosterone (DHT), an endogenous androgen. The androgen receptor agonistic activity of TSAA-291 was more obvious in reporter assays using skeletal muscle cells than in those using prostate cells. In castrated mice, TSAA-291 increased the weight of the levator ani muscle without increasing the weight of the prostate and seminal vesicle. Comprehensive cofactor recruitment analysis via mammalian two-hybrid methods revealed that among a total of 112 cofactors, 12 cofactors including the protein inhibitor of activated STAT 1 (PIAS1) were differently recruited to androgen receptor in the presence of TSAA-291 and DHT. Prostate displayed higher PIAS1 expression than skeletal muscle. Forced expressio...Continue Reading
References
Feb 1, 1987·Endocrine Reviews·A D MooradianS G Korenman
Jul 1, 1981·Steroids·K SudoR Nakayama
Jan 28, 1999·The Journal of Biological Chemistry·A M MoilanenJ J Palvimo
Jun 11, 1999·The Journal of Biological Chemistry·M E BradyC N Robson
Oct 16, 1999·The Journal of Clinical Endocrinology and Metabolism·A Negro-Vilar
Apr 26, 2000·The Journal of Biological Chemistry·M FuR G Pestell
May 17, 2000·Critical Reviews in Eukaryotic Gene Expression·J BodeC Mielke
Sep 26, 2000·Molecular and Cellular Biology·M KippF O Fackelmayer
Jul 6, 2001·Oncogene·M GrossK Shuai
Mar 30, 2002·Molecular Endocrinology·Helmut DotzlawAria Baniahmad
Mar 30, 2002·Science·Yongfeng Shang, Myles Brown
Apr 2, 2003·Urology·Celestia S Higano
Nov 25, 2003·The Aging Male : the Official Journal of the International Society for the Study of the Aging Male·L Gooren
Oct 7, 2006·Endocrinology·Jeffrey N MinerAndres Negro-Vilar
Nov 10, 2007·Endocrine·George F AllanScott G Lundeen
Jan 2, 2015·Nucleic Acids Research·Sari ToropainenJorma J Palvimo
Aug 1, 2010·Hormone Molecular Biology and Clinical Investigation·Kazutoshi YamanaVan Luu-The
Citations
Jan 16, 2016·Drug Testing and Analysis·Mario ThevisWilhelm Schänzer
Jul 13, 2016·Biochemical and Biophysical Research Communications·Kenta WatanabeChisato Miyaura
Dec 8, 2017·PloS One·Megumi MorimotoTakahito Hara
Feb 8, 2020·Pharmacology Research & Perspectives·Megumi MorimotoTakahito Hara