title: A novel Sry-downstream cellular event which preserves the readily available energy source of glycogen in mouse sex differentiation.
abstract: Sry is transiently activated in pre-Sertoli cells of the gonadal ridge to initiate testis differentiation in mice. In pre-Sertoli cells, however, the cellular events induced immediately after the onset of Sry expression remain largely unknown. Here we show that testis-specific glycogen accumulation in pre-Sertoli cells is one of the earliest cellular events downstream of Sry action. In developing XY gonads, glycogen accumulation starts to occur in pre-Sertoli cells from around 11.15 dpc (tail somite 14 stage) in a center-to-pole pattern similar to the initial Sry expression profile. Glycogen accumulation was also found in XX male gonads of Sry-transgenic embryos, but not in XX female gonads of wildtype embryos at any developmental stage. In vitro analyses using various culture conditions suggest that testis-specific glycogen deposition is a tissue-autonomous event that can be induced even in serum-free conditions and in a culture of gonadal explants without adjacent mesonephros. Moreover, glycogen accumulation in pre-Sertoli cells was significantly inhibited in vitro by the PI3K inhibitor LY294002, but not by the MEK inhibitor PD98059. Active phospho-AKT (PI3K effector) showed a high degree of accumulation in gonadal somatic cells of genital ridges in a testis-specific manner, both in vitro and in vivo. Therefore, these findings suggest that immediately after the onset of Sry expression, activation of the PI3K-AKT pathway promotes testis-specific glycogen storage in pre-Sertoli cells. To the best of our knowledge, this is a novel Sry-downstream cellular event which preserves this readily available energy source in Sertoli cells for testis-specific morphogenesis and hormone production.
authors.affiliation: Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Matoba
authors.forename: Yoshiakira
authors.initials: Y
authors.lastname: Kanai
authors.forename: Tomohide
authors.initials: T
authors.lastname: Kidokoro
authors.forename: Masami
authors.initials: M
authors.lastname: Kanai-Azuma
authors.forename: Hayato
authors.initials: H
authors.lastname: Kawakami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Masamichi
authors.initials: M
authors.lastname: Kurohmaru
mesh_terms: D000818:Animals; D002066:Busulfan / Q000494:pharmacology; D002468:Cell Physiological Phenomena / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006003:Glycogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D009924:Organ Culture Techniques / Q000379:methods; D009928:Organ Specificity / Q000502:physiology; D012708:Sertoli Cells / Q000378:metabolism; D012727:Sex Characteristics; D012732:Sex Determination Analysis; D012733:Sex Differentiation / Q000235:genetics; D051876:Sex-Determining Region Y Protein; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013737:Testis / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002867:Chromones; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009025:Morpholines; D009687:Nuclear Proteins; D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse; D014157:Transcription Factors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D006003:Glycogen; D002066:Busulfan