PMID- 11368421
OWN - NLM
STAT- MEDLINE
DCOM- 20010531
LR  - 20190607
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 226
IP  - 4
DP  - 2001 Apr
TI  - Coumestrol antagonizes neuroendocrine actions of estrogen via the estrogen 
      receptor alpha.
PG  - 301-6
AB  - The phytoestrogen coumestrol has estrogenic actions on peripheral reproductive 
      tissues. Yet in the brain this compound has both estrogenic and anti-estrogenic 
      effects. We used estrogen receptor alpha knockout mice (ERalphaKO) to determine 
      whether coumestrol has estrogenic actions in mice and also if these effects are 
      mediated by the classic ERalpha. Female wild-type (WT) and ERalphaKO mice were 
      ovariectomized and treated with estradiol (E2), dietary coumestrol, both, or 
      neither compound. Ten days later the animals were sacrificed, blood was 
      collected, and brain tissues were perfused. Fixed brains were sectioned and 
      immunocytochemistry was employed to quantify progesterone receptors (PR) in the 
      medial preoptic (POA) and ventromedial nucleus of the hypothalamus (VMN). Plasma 
      was assayed for luteinizing hormone (LH). Estrogen treatment induced PR 
      immunoreactivity in both regions in brains of WT females. In ERalphaKO mice, 
      lower levels of PR were induced. The stimulatory effects of E2 on PR were 
      attenuated in the POA by cotreatment with coumestrol, and the same trend was 
      noted in the VMN. WT ovariectomized females treated with E2 had low levels of LH, 
      while LH was high in untreated females and even higher in ovariectomized females 
      treated with coumestrol. ERalphaKO females in all treatment groups had high 
      levels of LH. Taken together, the results show that coumestrol has 
      anti-estrogenic actions in the brain and pituitary and that ERalpha mediates 
      these effects.
FAU - Jacob, D A
AU  - Jacob DA
AD  - Department of Biology and Neuroscience Program, University of Virginia, 
      Charlottesville 22904-4328, USA.
FAU - Temple, J L
AU  - Temple JL
FAU - Patisaul, H B
AU  - Patisaul HB
FAU - Young, L J
AU  - Young LJ
FAU - Rissman, E F
AU  - Rissman EF
LA  - eng
GR  - K02 MH01349/MH/NIMH NIH HHS/United States
GR  - R01 MH57759/MH/NIMH NIH HHS/United States
GR  - U54 HD28934/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogens, Non-Steroidal)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - V7NW98OB34 (Coumestrol)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Coumestrol/administration & dosage/*pharmacology
MH  - Drug Evaluation, Preclinical
MH  - Estradiol/administration & dosage/pharmacology
MH  - Estrogen Receptor alpha
MH  - Estrogens, Non-Steroidal/*pharmacology
MH  - Female
MH  - Hypothalamus/drug effects/metabolism
MH  - Luteinizing Hormone/blood
MH  - Mice
MH  - Mice, Knockout
MH  - Ovariectomy
MH  - Receptors, Estrogen/*antagonists & inhibitors/deficiency/genetics
MH  - Receptors, Progesterone/analysis
EDAT- 2001/05/23 10:00
MHDA- 2001/06/02 10:01
CRDT- 2001/05/23 10:00
PHST- 2001/05/23 10:00 [pubmed]
PHST- 2001/06/02 10:01 [medline]
PHST- 2001/05/23 10:00 [entrez]
AID - 10.1177/153537020122600406 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2001 Apr;226(4):301-6. doi: 10.1177/153537020122600406.