PMID- 23416106
OWN - NLM
STAT- MEDLINE
DCOM- 20131213
LR  - 20131021
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 137
DP  - 2013 Sep
TI  - Interaction of Androst-5-ene-3beta,17beta-diol and 5alpha-androstane-3beta,17beta-diol with 
      estrogen and androgen receptors: a combined binding and cell study.
PG  - 316-21
LID - S0960-0760(13)00017-4 [pii]
LID - 10.1016/j.jsbmb.2013.01.012 [doi]
AB  - Androst-5-ene-3beta,17beta-diol (ADIOL) and 5alpha-androstane-3beta,17beta-diol (3beta-DIOL), 
      metabolites of dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), 
      respectively, are known to possess estrogenic properties. To better understand 
      their hormonal action and roles in the proliferation of breast cancer (BC) cells, 
      we studied their binding to sex-hormone receptors in estrogen receptor 
      (ER)-positive (ZR-75-1 and T-47D) and ER-negative (MDA-MB-231) human BC cells. 
      The results demonstrated that estradiol (E2), ADIOL and 3beta-DIOL stimulated the 
      proliferation of ZR-75-1 and T-47D cells, but had no effect on ER-negative cells. 
      In the presence of estradiol, ADIOL and 3beta-DIOL inhibited the estrogen-stimulated 
      BC cell growth. This inhibition was counteracted by anti-androgens, which were 
      unable to affect the ADIOL and 3beta-DIOL stimulatory effects in E2-free medium. On 
      the other hand, in the presence of tamoxifen, ADIOL and 3beta-DIOL showed an 
      additional anti-proliferative activity on hormone-sensitive BC cells compared 
      with tamoxifen treatment alone. These results are similar to previous reports 
      obtained using MCF-7 cells, which confirmed that ADIOL and 3beta-DIOL stimulated 
      estrogen-dependent BC cell growth via ERs, but inhibited growth via androgen 
      receptors (ARs). Several steroids bind to both ER and AR in a different 
      preference and degree, i.e. E2>estrone (E1)>ADIOL>3beta-DIOL>testosterone (T)>DHT 
      for ER and DHT>T>3beta-DIOL>ADIOL>E1>E2 for AR. The relative binding affinities of 
      ADIOL, 3beta-DIOL, and E2 corresponded well to their respective potential in 
      stimulating cell proliferation of ZR-75-1 and T-47D cells in our results. The 
      intrinsic relationship between cell proliferation effects and binding affinities 
      for receptors of several steroids was revealed here by a combined binding and 
      cell study. This article is part of a Special Issue entitled 'Synthesis and 
      biological testing of steroid derivatives as inhibitors'.
CI  - Copyright (c) 2013. Published by Elsevier Ltd.
FAU - Chen, Jiong
AU  - Chen J
AD  - Laboratory of Structural Biology with Visiting Scientists, Institute of 
      Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, 
      Shanghai 200031, China.
FAU - Wang, Wei-Qi
AU  - Wang WQ
FAU - Lin, Sheng-Xiang
AU  - Lin SX
LA  - eng
GR  - MOP 89851/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130214
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Receptors, Androgen)
RN  - 0 (Receptors, Estrogen)
RN  - 25126-76-5 (Androstane-3,17-diol)
RN  - 95PS51EMXY (Androstenediol)
SB  - IM
MH  - Androstane-3,17-diol/*metabolism
MH  - Androstenediol/*metabolism
MH  - Cell Line, Tumor
MH  - Humans
MH  - Protein Binding
MH  - Receptors, Androgen/*metabolism
MH  - Receptors, Estrogen/*metabolism
OTO - NOTNLM
OT  - 3beta-DIOL
OT  - 5alpha-androstane-3beta,17beta-diol
OT  - ADIOL
OT  - AR
OT  - Androgens
OT  - Antiandrogens
OT  - Antiestrogens
OT  - BC
OT  - DHEA
OT  - DHT
OT  - E1
OT  - E2
OT  - ER
OT  - Estrogen receptors
OT  - Estrogens
OT  - Ligands
OT  - OH-flu
OT  - T
OT  - androgen receptor
OT  - androst-5-ene-3beta,17beta-diol
OT  - breast cancer
OT  - dehydroepiandrosterone
OT  - dihydrotestosterone
OT  - estradiol
OT  - estrogen receptor
OT  - estrone
OT  - hydroxyflutamine
OT  - testosterone
EDAT- 2013/02/19 06:00
MHDA- 2013/12/18 06:00
CRDT- 2013/02/19 06:00
PHST- 2012/11/27 00:00 [received]
PHST- 2013/01/04 00:00 [revised]
PHST- 2013/01/24 00:00 [accepted]
PHST- 2013/02/19 06:00 [entrez]
PHST- 2013/02/19 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
AID - S0960-0760(13)00017-4 [pii]
AID - 10.1016/j.jsbmb.2013.01.012 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2013 Sep;137:316-21. doi: 
      10.1016/j.jsbmb.2013.01.012. Epub 2013 Feb 14.