title: Antiestrogenic activity of vitamin A in in vivo uterotrophic assay.
abstract: All-trans-retinoic acid (ATRA), the primary active metabolite of vitamin A, was examined for its antiestrogenic activity in rats using an in vivo uterotrophic assay. All rats were ovariectomized 2 weeks prior to receiving 5 mg/kg/day ATRA or 0.3 micro g/kg/day ethynyl estradiol (EE) subcutaneously once a day for 3 consecutive days. Rats were sacrificed 1, 3, 6, 12 or 24 h after the last treatment. EE increased uterine weight and the coinjection of ATRA with EE significantly suppressed this effect 3 and 24 h after treatment. mRNA expression was examined during this 24-h period and the mRNA expression levels of estrogen receptor alpha (ER alpha), retinoic acid receptor beta (RAR beta), retinoid X receptor gamma (RXR gamma) and cellular retinol-binding protein I (CRBP I) were found to have significantly increased in the ATRA+EE group compared with those in the EE group. This is the first report on the antiestrogenic activity of ATRA determined using an in vivo adult rat uterotrophic assay. The up-regulation of RAR or RXR mRNA expression level was probably responsible for the antiestrogenic activity of ATRA.
authors.affiliation: Division of Environmental Health Sciences, Department of Social Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Japan. tk760131@med.miyazaki-u.ac.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Koda
authors.forename: Hideki
authors.initials: H
authors.lastname: Imai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Morita
mesh_terms: D000818:Animals; D045166:Estradiol Congeners / Q000494:pharmacology; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis; D047491:Retinoid X Receptor gamma / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D014599:Uterus / Q000187:drug effects*
chemical_list: D045166:Estradiol Congeners; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047491:Retinoid X Receptor gamma; C082927:retinoic acid binding protein I, cellular; D004997:Ethinyl Estradiol; D014212:Tretinoin