title: Analysis of the effects of oestrogen receptor alpha (ERalpha)- and ERbeta-selective ligands given in combination to ovariectomized rats.
abstract: OBJECTIVE
  Studies with oestrogen receptoralpha (ERalpha)- and ERbeta-selective compounds have already shown that the effects of 17beta-estradiol (E2) on body weight, movement drive and bone-protection are mediated via ERalpha. This study was based on the hypothesis that activation of ERbeta may antagonize ERalpha-mediated effects and designed to investigate potential effects of ERalpha/ERbeta heterodimers.
  
  
  METHODS
  Ovariectomized (OVX) female Wistar rats were treated with combinations of the ERalpha-specific agonist 16alpha-LE2 (ALPHA; 1 and 10 microg kg(-1) d(-1)), the ERbeta-specific agonist 8beta-VE2 (BETA; 100 microg kg(-1) d(-1)), the phytoestrogen, genistein (10 mg kg(-1) d(-1)) and with the anti-oestrogen compound, ICI 182,780 (3 mg kg(-1) d(-1)) for three weeks. The combined effects of the substances on body weight increase, tibial bone mineral density (BMD) and the influence on running wheel activity (RWA) were investigated.
  
  
  RESULTS
  OVX-induced body weight increase was reduced by co-administration of genistein and BETA. Co-application of BETA or genistein with ALPHA had no effect on ALPHA-mediated bone-protection. The RWA of OVX animals was significantly reduced by treatment with genistein but stimulated by application of ALPHA. The stimulatory effect of ALPHA on RWA could be antagonized by co-treatment with the pure antioestrogen ICI 182,780 but also by co-administration of genistein or BETA.
  
  
  CONCLUSIONS
  Our results indicate that activation of ERbeta may modulate ERalpha-mediated physiological effects in vivo. The observation that substances with selective affinity for ERbeta are able to antagonize distinct physiological functions, like RWA, may be of great relevance to the pharmaceutical use of such drugs.
authors.affiliation: Institut für Kreislaufforschung und Sportmedizin, Abt. molekulare und zelluläre Sportmedizin, DSHS Köln, Cologne, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hertrampf
authors.forename: J
authors.initials: J
authors.lastname: Seibel
authors.forename: U
authors.initials: U
authors.lastname: Laudenbach
authors.forename: K H
authors.initials: KH
authors.lastname: Fritzemeier
authors.forename: P
authors.initials: P
authors.lastname: Diel
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists*; D047629:Estrogen Receptor beta / Q000819:agonists*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D019833:Genistein / Q000494:pharmacology; D008024:Ligands; D009043:Motor Activity / Q000187:drug effects; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D008024:Ligands; D048789:Phytoestrogens; D000077267:Fulvestrant; D004958:Estradiol; D019833:Genistein