KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    MicroRNA-21 Mediated Post-Transcriptional Gene Regulation in Ovarian Function

    Thumbnail
    View/Open
    Carletti_ku_0099D_10510_DATA_1.pdf (10.54Mb)
    Issue Date
    2009-07-28
    Author
    Carletti, Martha Ziegler
    Publisher
    University of Kansas
    Format
    265 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Molecular & Integrative Physiology
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
    Metadata
    Show full item record
    Abstract
    The release of the oocyte from the ovary (ovulation) and terminal differentiation of cells of the preovulatory follicle (luteinization) are initiated by the surge of pituitary luteinizing hormone (LH) and are essential for proper reproductive function. As a result, major research efforts have been dedicated to deciphering the signaling pathways and transcriptional networks that are activated in granulosa cells following the LH surge. Remarkably however, few studies have examined the role post-transcriptional gene regulation plays in mediating LH action within preovulatory granulosa cells. Because cell and tissue function are reliant on the proper splicing, localization, and translation of mRNA to protein (i.e., post-transcriptional gene regulation) understanding this regulatory mechanism is essential for understanding ovarian (granulosa cell) function. MicroRNA (miRNA) mediate changes in post-transcriptional gene expression and have been tightly linked to a number of cell developmental and differentiation events. We identified miRNA-21 (miR-21) as an LH-induced miRNA in murine granulosa cells. The goal of this dissertation was to determine the function of miR-21 in granulosa cells of the periovulatory follicle. We found that in vitro knockdown of miR-21 in granulosa cells using antisense locked nucleic acid oligonucleotides (LNA) increased apoptotic death and decreased global translation, and these cellular events could be separated pharmacologically. Exogenous miR-21 increased global translation and our current evidence implicates changes in the activity of the Akt/mTOR pathways upstream of the critically important elongation factor-2 as the cause for this increase in protein synthesis. In vivo knockdown of miR-21 blocked ovulation and increased granulosa cell apoptosis. Therefore, miR-21 functions in periovulatory granulosa cells to inhibit apoptosis and to promote global translation, thus likely promoting the formation of a functional corpus luteum and allowing for the establishment and maintenance of pregnancy.
    URI
    http://hdl.handle.net/1808/5592
    Collections
    • Dissertations [4475]
    • Molecular Biosciences Dissertations and Theses [270]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps