title: Royal jelly has estrogenic effects in vitro and in vivo.
abstract: Royal jelly (RJ) from honeybees (Apis mellifera) is traditionally thought to improve menopausal symptoms. The potential estrogenic activities of RJ were investigated using various approaches. RJ competed for binding of 17beta-estradiol to the human estrogen receptor alpha and beta but its affinities were weak compared with diethylstilbestrol and phytoestrogens. The reporter gene expression assays suggested that 0.1-1 mg/ml RJ activated estrogen receptors, leading to enhanced transcription of a reporter gene through an estrogen-responsive element. 1 mg/ml RJ stimulated the mRNA expression of estrogen-responsive pS2 and vascular endothelial growth factor (VEGF) by increasing gene transcription in MCF-7 cells. Treatment with RJ at concentrations ranging from 0.5 to 1 mg/ml enhanced MCF-7 cell proliferation, but concomitant treatment with 1 microM tamoxifen blocked this effect. In vivo studies using ovariectomized rats showed that 17beta-estradiol (20 mg/kg, s.c.) treatment restored VEGF expression in both uterus and brain, whereas RJ (1 g/kg, s.c.) restored it in uterus but not in brain. These findings provide evidence that RJ has estrogenic activities through interaction with estrogen receptors followed by endogenous gene expressions.
authors.affiliation: Nagaragawa Research Center, API Co., Ltd., 692-3 Nagara, Gifu 502-0071, Japan. mishima-satoshi@api3838.co.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mishima
authors.forename: Kazu-Michi
authors.initials: KM
authors.lastname: Suzuki
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Isohama
authors.forename: Naoko
authors.initials: N
authors.lastname: Kuratsu
authors.forename: Yoko
authors.initials: Y
authors.lastname: Araki
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000378:metabolism; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D000099219:Royal Jelly
chemical_list: D004967:Estrogens; D005227:Fatty Acids; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D000099219:Royal Jelly; C051838:TFF1 protein, human