title: EGR2 is a gonadotropin-induced survival factor that controls the expression of IER3 in ovarian granulosa cells.
abstract: Pituitary gonadotropins are key hormones that orchestrate the growth and development of ovarian follicles. However, limited information is available on intra-ovarian factors that mediate the actions of gonadotropins. In this study, we identified that the early growth response 2 gene (EGR2) is a gonadotropin-inducible gene in granulosa cells of rats and humans. Analysis of consensus EGR-binding elements (EBEs) showed that the immediate early response 3 gene (IER3) is a novel transcriptional target gene of EGR2 as confirmed by the luciferase assay, electrophoretic mobility-shift assay (EMSA), chromatin immunoprecipitation (ChIP), and western blot analysis. Overexpression of EGR2 promoted survival of KGN human granulosa-derived cells in which IER3 acts as a mediator; knockdown of EGR2 induced death in KGN cells. Additionally, EGR2 was found to regulate the expression of myeloid cell leukemia 1 (MCL-1), which belongs to the BCL-2 family of proteins regulating cell survival. Thus, this study identified a novel signaling axis, comprised of gonadotropins-EGR2-IER3, which is important for the survival of granulosa cells during folliculogenesis.
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul 06974, South Korea.
authors.forename: Hanyong
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Pharmacy, CHA University, Seongnam 13488, South Korea.
authors.forename: Miae
authors.initials: M
authors.lastname: Won
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul 06974, South Korea.
authors.forename: Eunkyoung
authors.initials: E
authors.lastname: Shin
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 06974, South Korea.
authors.forename: Hong-Man
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul 06974, South Korea.
authors.forename: Kangseok
authors.initials: K
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Chung-Ang University, Seoul 06974, South Korea. Electronic address: jeehyeon@cau.ac.kr.
authors.forename: Jeehyeon
authors.initials: J
authors.lastname: Bae
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival; D051767:Early Growth Response Protein 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006062:Gonadotropins / Q000378:metabolism*; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation
chemical_list: D051017:Apoptosis Regulatory Proteins; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; C497328:Egr2 protein, rat; D006062:Gonadotropins; C099815:IER3 protein, human; C000619666:IER3 protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger
keywords: FSH; KROX20; LH; Target gene; Transcriptional regulation