title: Estrogen-regulated prohibitin is required for mouse uterine development and adult function.
abstract: Estrogen signaling is pivotal for maintenance of female reproductive function in mammals. The physiological role of estrogen is mediated by estrogen receptors (ERs) and the steroid receptor coactivator family of transcriptional coregulators. Ablation of steroid receptor coactivator and ER coactivators in mice causes impaired female reproductive function. Recently we reported that prohibitin (PHB) can function as a corepressor for ERs in cultured cells. In this study, we demonstrate that PHB is an estrogen-regulated gene in vitro and in vivo, and its expression is induced by estrogen in the uterus, suggesting the existence of feedback regulatory loops. A conditional PHB knockout mouse model was generated by gene targeting to assess its in vivo function. Female mice with selective ablation of the PHB allele in the uterus were sterile, and their uteri were severely hypoplastic, indicating PHB is required for uterine development. Moreover, expression of ER and progesterone receptor target genes was selectively altered in response to hormone treatment. In summary, this study demonstrates that PHB is an estrogen-regulated gene and that PHB is essential for mouse uterine development and adult function and selectively required for estrogen-regulated gene expression.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Kommagani
authors.forename: Qin
authors.initials: Q
authors.lastname: Feng
authors.forename: Rainer B
authors.initials: RB
authors.lastname: Lanz
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: DeMayo
authors.forename: Benita S
authors.initials: BS
authors.lastname: Katzenellenbogen
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
mesh_terms: D000483:Alleles; D000818:Animals; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D004967:Estrogens / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D051379:Mice; D009154:Mutation; D000091402:Prohibitins; D011555:Pseudopregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014599:Uterus / Q000254:growth & development* / Q000378:metabolism
chemical_list: D004967:Estrogens; C000717328:PHB protein, human; D000091402:Prohibitins; D012333:RNA, Messenger; D012097:Repressor Proteins