PMID- 22266284
OWN - NLM
STAT- MEDLINE
DCOM- 20120622
LR  - 20220105
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 130
IP  - 1-2
DP  - 2012 May
TI  - Estrogen receptor-beta agonist diarylpropionitrile counteracts the estrogenic 
      activity of estrogen receptor-alpha agonist propylpyrazole-triol in the mammary 
      gland of ovariectomized Sprague Dawley rats.
PG  - 26-35
LID - 10.1016/j.jsbmb.2011.12.018 [doi]
AB  - Although estrogen can bind both types of estrogen receptors, estrogen 
      receptor-alpha (ERalpha) is dominant in mediating estrogenic activity in the mammary 
      gland and uterus. Excessive estrogenic activity such as estrogen-based 
      postmenopausal hormone replacement therapy increases the risk for breast and 
      endometrial cancers. The adverse effect of estrogen on uterine endometrium can be 
      opposed by progestins; however, estrogen-plus-progestin regimen imposes 
      substantially greater risk for breast cancer than estrogen alone. In this study, 
      we used ERalpha-selective agonist propylpyrazole-triol (PPT) and ERbeta-selective 
      agonist diarylpropionitrile (DPN) to activate ERalpha and estrogen receptor-beta 
      (ERbeta) separately in an ovariectomized rat model and determined whether 
      PPT-activated ERalpha function in the mammary gland can be suppressed by DPN 
      activated ERbeta. Ovariectomized rats were randomly divided into six groups and 
      treated with DMSO (control), DPN, PPT, PPT/DPN, PPT/Progesterone, and 
      PPT/Progesterone/DPN, respectively. In the mammary gland, PPT but not DPN 
      increased cell proliferation and amphiregulin gene expression; importantly, the 
      stimulatory effect of PPT on mammary cell proliferation and amphiregulin gene 
      expression can be suppressed by DPN. In the uterus, the effect of PPT on uterine 
      weight and endometrial cell proliferation was not inhibited by DPN but can be 
      inhibited by progesterone. These data provide in vivo evidence that PPT activated 
      ERalpha activity in the mammary gland can be opposed by ERbeta-selective agonist DPN, 
      which may be explored for the development of better hormone replacement therapy 
      regimen with less risk for breast cancer.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Song, Xiaozheng
AU  - Song X
AD  - Department of Animal Science, Vermont Cancer Center, University of Vermont, 
      Burlington, VT 05405, USA.
FAU - Pan, Zhong-Zong
AU  - Pan ZZ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120114
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (2,3-bis(4-hydroxyphenyl)-propionitrile)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Nitriles)
RN  - 0 (Phenols)
RN  - 0 (Propionates)
RN  - 0 (Pyrazoles)
RN  - 0T83Y6JZPF (4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol)
SB  - IM
MH  - Animals
MH  - Cell Proliferation
MH  - Estrogen Receptor alpha/*agonists/*metabolism
MH  - Estrogen Receptor beta/*agonists/*metabolism
MH  - Female
MH  - Immunohistochemistry
MH  - Mammary Glands, Animal/drug effects/metabolism
MH  - Nitriles/metabolism/*pharmacology
MH  - Ovariectomy
MH  - Phenols
MH  - Propionates/metabolism/*pharmacology
MH  - Pyrazoles/metabolism/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2012/01/24 06:00
MHDA- 2012/06/23 06:00
CRDT- 2012/01/24 06:00
PHST- 2011/08/25 00:00 [received]
PHST- 2011/12/23 00:00 [revised]
PHST- 2011/12/27 00:00 [accepted]
PHST- 2012/01/24 06:00 [entrez]
PHST- 2012/01/24 06:00 [pubmed]
PHST- 2012/06/23 06:00 [medline]
AID - S0960-0760(11)00260-3 [pii]
AID - 10.1016/j.jsbmb.2011.12.018 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2012 May;130(1-2):26-35. doi: 
      10.1016/j.jsbmb.2011.12.018. Epub 2012 Jan 14.