Prolactin signaling through the short form of its receptor represses forkhead transcription factor FOXO3 and its target gene galt causing a severe ovarian defect
| Autor: | Diane Rebourcet, Sangeeta Y. Devi, Nadine Binart, Carlos Stocco, Nancy D. Leslie, Geula Gibori, Julia Halperin, Aurora Shehu, Jamie Le, Terry G. Unterman, Shai E. Elizur |
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| Přispěvatelé: | Department of Physiology and Biophysics, College of Medicine of Chicago, Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Medecine, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Cincinnati Children's Hospital Medical Center, Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of Illinois at Chicago ( UIC ) |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
MESH: Signal Transduction
endocrine system diseases Transcription Genetic MESH : Genotype Electrophoretic Mobility Shift Assay MESH : Blotting Western MESH: Mice Knockout MESH: Genotype Mice Endocrinology Ovarian Follicle MESH : Prolactin MESH: Reverse Transcriptase Polymerase Chain Reaction MESH : Female MESH: Animals [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics Receptor Mice Knockout Regulation of gene expression MESH : Gene Expression Regulation Reverse Transcriptase Polymerase Chain Reaction Forkhead Box Protein O3 MESH : Reverse Transcriptase Polymerase Chain Reaction Forkhead Transcription Factors General Medicine MESH: Gene Expression Regulation MESH : Mice Transgenic Premature ovarian failure Cell biology MESH : Forkhead Transcription Factors medicine.anatomical_structure MESH : Electrophoretic Mobility Shift Assay FOXO3 Female Signal transduction Signal Transduction MESH: Ovary medicine.medical_specialty endocrine system MESH: Cell Line Tumor Genotype Receptors Prolactin MESH: Mice Transgenic MESH : Ovarian Follicle Blotting Western MESH: Prolactin Mice Transgenic Ovary Biology Article MESH: Receptors Prolactin MESH: Forkhead Transcription Factors Cell Line Tumor Internal medicine MESH : Mice medicine Animals Humans UTP-Hexose-1-Phosphate Uridylyltransferase MESH: Blotting Western Ovarian follicle Molecular Biology Transcription factor MESH: Mice MESH : Receptors Prolactin MESH : Ovary MESH : Signal Transduction MESH: Humans MESH: UTP-Hexose-1-Phosphate Uridylyltransferase MESH : Cell Line Tumor MESH: Transcription Genetic MESH : Humans MESH : Transcription Genetic MESH : UTP-Hexose-1-Phosphate Uridylyltransferase medicine.disease MESH: Ovarian Follicle Prolactin Gene Expression Regulation [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics MESH: Electrophoretic Mobility Shift Assay MESH : Mice Knockout MESH : Animals MESH: Female |
| Zdroj: | Molecular Endocrinology-Baltimore Molecular Endocrinology-Baltimore-, Endocrine Society, 2008, 22 (2), pp.513-22. ⟨10.1210/me.2007-0399⟩ Molecular Endocrinology-Baltimore-, Endocrine Society, 2008, 22 (2), pp.513-22. 〈10.1210/me.2007-0399〉 |
| ISSN: | 0888-8809 |
| DOI: | 10.1210/me.2007-0399⟩ |
| Popis: | Prolactin (PRL) is a hormone with over 300 biological activities. Although the signaling pathway downstream of the long form of its receptor (RL) has been well characterized, little is known about PRL actions upon activation of the short form (RS). Here, we show that mice expressing only RS exhibit an ovarian phenotype of accelerated follicular recruitment followed by massive follicular death leading to premature ovarian failure. Consequently, RS-expressing ovaries of young adults are depleted of functional follicles and formed mostly by interstitium. We also show that activation of RS represses the expression of the transcription factor Forkhead box O3 (FOXO3) and that of the enzyme galactose-1-phosphate uridyltransferase (Galt), two proteins known to be essential for normal follicular development. Our finding that FOXO3 regulates the expression of Galt and enhances its transcriptional activity indicates that it is the repression of FOXO3 by PRL acting through RS that prevents Galt expression in the ovary and causes follicular death. Coexpression of RL with RS prevents PRL inhibition of Galt, and the ovarian defect is no longer seen in RS transgenic mice that coexpress RL, suggesting that RL prevents RS-induced ovarian impairment. In summary, we show that PRL signals through RS and causes, in the absence of RL, a severe ovarian pathology by repressing the expression of FOXO3 and that of its target gene Galt. We also provide evidence of a link between the premature ovarian failure seen in mice expressing RS and in mice with FOXO3 gene deletion as well as in human with Galt mutation. |
| Databáze: | OpenAIRE |
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