PMID- 11836071
OWN - NLM
STAT- MEDLINE
DCOM- 20020620
LR  - 20190922
IS  - 0892-0362 (Print)
IS  - 0892-0362 (Linking)
VI  - 24
IP  - 1
DP  - 2002 Jan-Feb
TI  - Neurobehavioral actions of coumestrol and related isoflavonoids in rodents.
PG  - 47-54
AB  - Isoflavonoids are plant estrogens that are increasingly advocated as a natural 
      alternative to estrogen replacement therapy (ERT) and are available as dietary 
      supplements. As weak estrogen agonists/antagonists with a range of other 
      enzymatic activities, the isoflavonoids provide a useful model for the actions of 
      endocrine disruptors. This paper reviews the responses of rodents to diets 
      containing coumestrol or an isoflavone supplement in comparison to animals fed 
      the phytoestrogen-free AIN76A diet. Neural mechanisms were investigated by 
      examining isoflavonoid effects on ER(alpha)-dependent (regulation of oxytocin 
      receptor [OTR] binding in the ventromedial nucleus of the hypothalamus [VMN]) and 
      ERbeta-dependent (regulation of ERbeta mRNA in the paraventricular nucleus [PVN]) 
      endpoints. Activational as well as organizational effects on sexual behavior and 
      gonadotropin secretion were observed for coumestrol. Treatment of rat dams with a 
      100-ppm coumestrol diet from birth to postnatal day (PND) 21 induced premature 
      anovulation in female offspring, and treatment from birth to PND 10 suppressed 
      sexual behavior in male offspring. One-week treatment of ovariectomized (OVX) 
      female rats with the same coumestrol diet increased ERbeta mRNA expression in the 
      PVN, an effect opposite to that of estradiol. Ten days of treatment with a 
      200-ppm coumestrol diet increased LH secretion in OVX wild-type mice, an effect 
      opposite to the normal negative feedback effects of estradiol. No effects were 
      observed in ER(alpha) knockout (ER(alpha)KO)-OVX females, indicating that 
      coumestrol's action on LH was mediated through ER(alpha). Similar activational 
      effects were observed for the isoflavone diet. The lordotic response to estrogen 
      was significantly reduced by 2 days of treatment of OVX adult females with an 
      isoflavone diet providing 13 ppm genistein and 33 ppm daidzein. One week of 
      treatment with the same isoflavone diet produced an effect opposite to that of 
      estradiol in the PVN, increasing ERbeta mRNA expression above control levels. 
      These investigations show that, in spite of their preferential affinity for 
      ERbeta, isoflavonoids act through both ER(alpha) and ERbeta. Moreover, their 
      neurobehavioral actions were antiestrogenic, either antagonizing or producing an 
      action in opposition to that of estradiol. This work demonstrates that even 
      small, physiologically relevant exposure levels can alter estrogen-dependent gene 
      expression in the brain and complex behavior.
FAU - Whitten, Patricia L
AU  - Whitten PL
AD  - Center for Behavioral Neuroscience, Emory University, Atlanta, GA 30329, USA. 
      antpw@emory.edu
FAU - Patisaul, Heather B
AU  - Patisaul HB
FAU - Young, Larry J
AU  - Young LJ
LA  - eng
GR  - ES04297/ES/NIEHS 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.
PT  - Review
PL  - United States
TA  - Neurotoxicol Teratol
JT  - Neurotoxicology and teratology
JID - 8709538
RN  - 0 (Estrogens, Non-Steroidal)
RN  - 0 (Isoflavones)
RN  - 0 (Receptors, Estrogen)
RN  - V7NW98OB34 (Coumestrol)
SB  - IM
MH  - Animals
MH  - Animals, Suckling
MH  - Coumestrol/*pharmacology
MH  - Estrogens, Non-Steroidal/*pharmacology
MH  - Female
MH  - Gene Expression/drug effects
MH  - Isoflavones/*pharmacology
MH  - Male
MH  - Mice
MH  - Rats
MH  - Receptors, Estrogen/genetics
MH  - Sexual Behavior, Animal/*drug effects
RF  - 33
EDAT- 2002/02/12 10:00
MHDA- 2002/06/21 10:01
CRDT- 2002/02/12 10:00
PHST- 2002/02/12 10:00 [pubmed]
PHST- 2002/06/21 10:01 [medline]
PHST- 2002/02/12 10:00 [entrez]
AID - S0892036201001921 [pii]
AID - 10.1016/s0892-0362(01)00192-1 [doi]
PST - ppublish
SO  - Neurotoxicol Teratol. 2002 Jan-Feb;24(1):47-54. doi: 
      10.1016/s0892-0362(01)00192-1.