title: Bmp7 and Lef1 are the downstream effectors of androgen signaling in androgen-induced sex characteristics development in medaka.
abstract: Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgen-dependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.
authors.affiliation: Okazaki Institute for Integrative Bioscience (Y.O., I.H., E.S., S.M., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, and Department of Basic Biology (Y.O., I.H., E.S., S.M., T.I.), Faculty of Life Science, The Graduate University for Advanced Studies, Aichi 444-8787, Japan; Department of Biological Information (K.I.), Tokyo Institute of Technology, Yokohama 226-8501, Japan; Department of Physiological Sciences (N.D.), Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida 32611; Department of Developmental Genetics (G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; and National Institute for Environmental Studies (N.T.), Ibaraki, 305-8506, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ogino
authors.forename: Ikumi
authors.initials: I
authors.lastname: Hirakawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Inohaya
authors.forename: Eri
authors.initials: E
authors.lastname: Sumiya
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Nancy
authors.initials: N
authors.lastname: Denslow
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
authors.forename: Norihisa
authors.initials: N
authors.lastname: Tatarazako
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D008297:Male; D008777:Methyltestosterone / Q000494:pharmacology; D009990:Oryzias / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012733:Sex Differentiation / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D055419:Bone Morphogenetic Protein 7; D051821:Lymphoid Enhancer-Binding Factor 1; D011944:Receptors, Androgen; D005485:Flutamide; D008777:Methyltestosterone