title: Estrogen receptor signaling protects against immune suppression by UV radiation exposure.
abstract: The phytoestrogenic isoflavonoid equol is known to protect against solar-simulated UV radiation-induced inflammation, immunosuppression, and skin carcinogenesis. The mechanism may involve antioxidant actions, because equol not only is a radical scavenger but also enhances the induction of a relevant cutaneous antioxidant, metallothionein. However, this study in female hairless mice examined whether the estrogenicity of the isoflavonoid might be responsible. Protection by topically applied equol against photoimmune suppression was found to be strongly and dose-dependently inhibited by the estrogen receptor (ER) antagonist ICI 182,780. Furthermore, ICI 182,780 alone was found to significantly exacerbate immunosuppression resulting from solar-simulated UV radiation irradiation, suggesting a natural role for the ER in photoimmune protection. In support of this role, topical application of the physiological ligand 17-beta-estradiol also provided dose-dependent photoimmune protection, inhibitable by ICI 182,780, that was attributed largely to the inactivation of the downstream actions of cis-urocanic acid, an important endogenous immunosuppressive photoproduct. Thus, a hitherto unrecognized function of the ER as a normal photoprotective immune regulator in the skin was revealed. The relationship between equol and cutaneous metallothionein suggests an association of the ER with this inducible antioxidant in constraining the photoimmune-suppressed state and therefore in the prevention of the facilitation of photocarcinogenesis by this immunological defect. This role for the ER may underlie important gender-specific differences in UV-responsiveness that would reflect different needs for environmental photoprotection in males and females.
authors.affiliation: Faculty of Veterinary Science, University of Sydney, McMaster Building B14, Sydney NSW 2006, Australia.
authors.forename: Sitarina
authors.initials: S
authors.lastname: Widyarini
authors.forename: Diane
authors.initials: D
authors.lastname: Domanski
authors.forename: Nicole
authors.initials: N
authors.lastname: Painter
authors.forename: Vivienne E
authors.initials: VE
authors.lastname: Reeve
mesh_terms: D000818:Animals; D019610:Cytoprotection; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D060754:Equol; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D007165:Immunosuppression Therapy; D007529:Isoflavones / Q000494:pharmacology; D051379:Mice; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D007529:Isoflavones; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D060754:Equol; D014560:Urocanic Acid