title: Premature ovarian failure in androgen receptor-deficient mice.
abstract: Premature ovarian failure (POF) syndrome, an early decline of ovarian function in women, is frequently associated with X chromosome abnormalities ranging from various Xq deletions to complete loss of one of the X chromosomes. However, the genetic locus responsible for the POF remains unknown, and no candidate gene has been identified. Using the Cre/LoxP system, we have disrupted the mouse X chromosome androgen receptor (Ar) gene. Female AR(-/-) mice appeared normal but developed the POF phenotype with aberrant ovarian gene expression. Eight-week-old female AR(-/-) mice are fertile, but they have lower follicle numbers and impaired mammary development, and they produce only half of the normal number of pups per litter. Forty-week-old AR(-/-) mice are infertile because of complete loss of follicles. Genome-wide microarray analysis of mRNA from AR(-/-) ovaries revealed that a number of major regulators of folliculogenesis were under transcriptional control by AR. Our findings suggest that AR function is required for normal female reproduction, particularly folliculogenesis, and that AR is a potential therapeutic target in POF syndrome.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shiina
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Igarashi
authors.forename: Junko
authors.initials: J
authors.lastname: Miyamoto
authors.forename: Sayuri
authors.initials: S
authors.lastname: Takemasa
authors.forename: Matomo
authors.initials: M
authors.lastname: Sakari
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takada
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D007150:Immunohistochemistry; D008156:Luciferases; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D006080:Ovarian Follicle / Q000033:anatomy & histology / Q000254:growth & development*; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D011944:Receptors, Androgen / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014960:X Chromosome / Q000235:genetics*
chemical_list: D011944:Receptors, Androgen; D008156:Luciferases