title: The hop phytoestrogen, 8-prenylnaringenin, reverses the ovariectomy-induced rise in skin temperature in an animal model of menopausal hot flushes.
abstract: The mechanisms underlying menopausal hot flushes are poorly understood, although it is generally assumed they result from disturbances of thermoregulatory centres in the hypothalamus. 8-Prenylnaringenin (8-PN) has been identified as a potent phytoestrogen in hops (Humulus lupulus) and there are claims that hop-containing preparations can reduce hot flushes. We have investigated the site of action of 8-PN in a rat model of menopausal hot flushes, in which the tail skin temperature (TST) is increased after oestrogen withdrawal induced by ovariectomy. Daily s.c. administration of either 17beta-oestradiol (E2; 4 microg/kg) or 8-PN (400 microg/kg) significantly reduced the elevated TST after 2 days of treatment. Subcutaneous co-administration of either E2 or 8-PN with the oestrogen receptor (ER) antagonist, ICI 182,780 (200 microg/kg), which is thought not to cross the blood-brain barrier, completely blocked the effect of E2 and 8-PN on TST. The ERalpha- and ERbeta-specific agonists, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (100 microg/kg) and 2,3-bis(4-hydroxyphenyl)-propionitrile (60 microg/kg) respectively, both significantly reversed the raised TST in ovariectomised rats. These observations suggest that the regulation of the vasomotor response by oestrogens and phytoestrogens is mediated, at least in part, by peripheral mechanisms involving both ERalpha and ERbeta.
authors.affiliation: Division of Reproduction and Endocrinology, King's College London, 2.36D New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors.forename: James
authors.initials: J
authors.lastname: Bowe
authors.forename: Xiao Feng
authors.initials: XF
authors.lastname: Li
authors.forename: James
authors.initials: J
authors.lastname: Kinsey-Jones
authors.forename: Arne
authors.initials: A
authors.lastname: Heyerick
authors.forename: Susan
authors.initials: S
authors.lastname: Brain
authors.forename: Stuart
authors.initials: S
authors.lastname: Milligan
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Byrne
mesh_terms: D000818:Animals; D001515:Beer; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists; D047629:Estrogen Receptor beta / Q000819:agonists; D005260:Female; D044950:Flavanones / Q000627:therapeutic use*; D000077267:Fulvestrant; D019584:Hot Flashes / Q000188:drug therapy*; D027582:Humulus; D023421:Models, Animal; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D010636:Phenols / Q000494:pharmacology; D008517:Phytotherapy; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012881:Skin Temperature / Q000187:drug effects*; D013623:Tail; D011422:Propionates
chemical_list: D004958:Estradiol; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D044950:Flavanones; D000077267:Fulvestrant; D009570:Nitriles; D010636:Phenols; D011720:Pyrazoles; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C119737:8-prenylnaringenin; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol