Estrogen and phytoestrogen regulate the mRNA expression of adrenomedullin and adrenomedullin receptor components in the rat uterus.
The serum estrogen surge in the uterus triggers precisely-timed physiological and biochemical responses required establishing and maintaining pregnancy. Previous reports have shown that consumption of phytoestrogen-containing plants may disrupt the precise control of pregnancy. To evaluate the effects of phytoestrogens in the uterus, we screened for estradiol (E2)-inducible genes in immature rat uteri. We identified the gene for receptor-activity-modifying protein 2 (Ramp2), known to be a component of the adrenomedullin (ADM) receptor, as responsive to both E2 and the phytoestrogen coumestrol (Cou). We further examined the expression of ADM and ADM signaling components Ramp2, Ramp3, and CRLR in the immature rat uterus and found that both E2 and Cou regulated these genes expression. In addition, treatment with ADM increased uterine weight and edema similar to that observed after Cou treatment. Our findings indicated that the phytoestrogen caused the abnormal induction of vasoactive factors in the uterus.
Department of Environmental Medicine, Center for Community Medicine, Jichi Medical School, Yakushiji 3311-1, Minamikawachi-machi, Kawachi-gun, Tochigi 329-0498, Japan.
Kazuhiro
K
Ikeda
Yukitomo
Y
Arao
Hiroko
H
Otsuka
Atsumi
A
Kikuchi
Fujio
F
Kayama
D053607:Adrenomedullin; D000818:Animals; D058286:Calcitonin Receptor-Like Protein; D003375:Coumestrol / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology; D004971:Estrus / Q000502:physiology; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D048789:Phytoestrogens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000235:genetics*; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D058286:Calcitonin Receptor-Like Protein; C545580:Calcrl protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; D048789:Phytoestrogens; D012333:RNA, Messenger; C545509:Ramp2 protein, rat; C545510:Ramp3 protein, rat; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin; D018000:Receptors, Peptide; D053607:Adrenomedullin; D000077267:Fulvestrant; D004958:Estradiol; D003375:Coumestrol