title: Egr1 is rapidly and transiently induced by estrogen and bisphenol A via activation of nuclear estrogen receptor-dependent ERK1/2 pathway in the uterus.
abstract: Coordinate actions of ovarian estrogen (E2) and progesterone (P4) via their own receptors are critical for establishing uterine receptivity for embryo implantation in the uterus. E2 regulates expression of an array of genes to mediate its major actions on heterogeneous uterine cell types. Here we have investigated regulatory mechanism(s) of E2 and bisphenol A (BPA), an endocrine disruptor with potent estrogenic activity on expression of early growth response 1 (Egr1), a zinc finger transcription factor that regulates cell growth, differentiation and apoptosis in the uterus. Egr1 was rapidly and transiently induced by E2 and BPA mainly in stromal cells via nuclear estrogen receptor (ER)-ERK1/2 pathway. ICI 182,780, an ER antagonist, effectively inhibited their actions on EGR1 expression following ERK1/2 phosphorylation. Administration of pharmacological inhibitors for ERK1/2, but not AKT significantly blocked EGR1 expression induced by E2 and BPA. P4 effectively dampened action(s) of E2 and BPA on Egr1 expression via nuclear progesterone receptor. Its antagonistic effects were partially interfered with RU486 pretreatment. Interestingly, EGR1 is specifically induced in stromal cells surrounding implanting blastocyst. Collectively, our results show that through nuclear ER-dependent ERK1/2 phosphorylation, not only E2 but also endocrine disruptors with estrogenic activity such as BPA rapidly and transiently induce Egr1 which may be important for embryo implantation and decidualization in mouse uterus.
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul 135-081, Republic of Korea.
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul 135-081, Republic of Korea.
authors.forename: Yeon Sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul 135-081, Republic of Korea.
authors.forename: Jung Ah
authors.initials: JA
authors.lastname: Yoon
authors.affiliation: Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul 135-081, Republic of Korea.
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Lyu
authors.affiliation: Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Shin
authors.affiliation: Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hyunjung J
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Kangwon National University, Chuncheon, Kangwon 200-701, Republic of Korea; Stem Cell Institute, Kangwon National University, Chuncheon, Kangwon 200-701, Republic of Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul 135-081, Republic of Korea.
authors.forename: Dong Ryul
authors.initials: DR
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul 135-081, Republic of Korea; Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul 135-081, Republic of Korea. Electronic address: hssong@cha.ac.kr.
authors.forename: Haengseok
authors.initials: H
authors.lastname: Song
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000502:physiology*; D051776:Early Growth Response Protein 3 / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005260:Female; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D010636:Phenols / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011960:Receptors, Estrogen / Q000502:physiology*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D051766:Early Growth Response Protein 1; D051776:Early Growth Response Protein 3; D004967:Estrogens; D048049:Extracellular Signal-Regulated MAP Kinases; D010636:Phenols; D011374:Progesterone; D051057:Proto-Oncogene Proteins c-akt; D011960:Receptors, Estrogen; C486109:Egr1 protein, mouse; C497369:Egr3 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; ERK1/2; Early growth response 1; Estrogen; Estrogen receptor; Uterus