title: Tissue specificity of 8-prenylnaringenin: protection from ovariectomy induced bone loss with minimal trophic effects on the uterus.
abstract: Plant secondary metabolites with estrogenic activity (phyto-estrogens) have been studied in the past as a potential alternative to classical hormone-replacement therapy (HRT) in menopausal women. No final verdict on the efficacy of soy or red clover based pharmaceutical preparations has been reached despite numerous clinical studies. We have studied the novel and most potent phyto-estrogen 8-prenylnaringenin (8-PN) in adult ovariectomized rats, an established animal model to mimic hormone dependent osteoporosis in menopausal women. Our results demonstrate that 8-PN can completely protect from ovariectomy induced bone-loss while exhibiting minimal, (dose independent) trophic effects on uterus and endometrium. It is estimated that at equivalent bone protective doses of 17beta-estradiol and 8-PN, the phyto-estrogen has a 10-fold lower stimulatory effect on uterus and endometrium. The bone tissue specific effect of 8-PN was confirmed in a transgenic reporter mouse model (ERE-Luc mice). Here we also found pronounced estrogenic activity in prostate. Present results add important aspects to the pharmacological profile of 8-PN and position this compound as an interesting alternative new candidate for treatment of peri- and postmenopausal symptoms.
authors.affiliation: Research Laboratories Schering AG, Berlin, Germany. michael.huempl@schering.de
authors.forename: Michael
authors.initials: M
authors.lastname: Hümpel
authors.forename: Päivi
authors.initials: P
authors.lastname: Isaksson
authors.forename: Olaf
authors.initials: O
authors.lastname: Schaefer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kaufmann
authors.forename: Paolo
authors.initials: P
authors.lastname: Ciana
authors.forename: Adriana
authors.initials: A
authors.lastname: Maggi
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Schleuning
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology / Q000627:therapeutic use*; D011467:Prostate / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects*
chemical_list: C119737:8-prenylnaringenin; D044950:Flavanones; D048789:Phytoestrogens; D004958:Estradiol