Pro-nerve growth factor in the ovary and human granulosa cells

Sabine Meinel, Jan Blohberger, Dieter Berg, Ulrike Berg, Gregory Dissen, Sergio Ojeda, Artur Mayerhofer

    Research output: Contribution to journalArticle

    3 Scopus citations

    Abstract

    Background: Pro-nerve growth factor must be cleaved to generate mature NGF, which was suggested to be a factor involved in ovarian physiology and pathology. Extracellular proNGF can induce cell death in many tissues. Whether extracellular proNGF exists in the ovary and may play a role in the death of follicular cells or atresia was unknown. Materials and methods: Immunohistochemistry of human and rhesus monkey ovarian sections was performed. IVF-derived follicular fluid and human granulosa cells were studied by RT-PCR, qPCR, Western blotting, ATP- and caspase-assays. Results and conclusion: Immunohistochemistry of ovarian sections identified proNGF in granulosa cells and Western blotting of human isolated granulosa cells confirmed the presence of proNGF. Ovarian granulosa cells thus produce proNGF. Recombinant human proNGF even at high concentrations did not affect the levels of ATP or the activity of caspase 3/7, indicating that in granulosa cells proNGF does not induce death. In contrast, mature NGF, which was detected previously in follicular fluid, may be a trophic molecule for granulosa cells with unexpected functions. We found that in contrast to proNGF, NGF increased the levels of the transcription factor early growth response 1 and of the enzyme choline acetyl-transferase. A mechanism for the generation of mature NGF from proNGF in the follicular fluid may be extracellular enzymatic cleavage. The enzyme MMP7 is known to cleave proNGF and was identified in follicular fluid and as a product of granulosa cells. Thus the generation of NGF in the ovarian follicle may depend on MMP7.

    Original languageEnglish (US)
    Pages (from-to)91-99
    Number of pages9
    JournalHormone Molecular Biology and Clinical Investigation
    Volume24
    Issue number2
    DOIs
    StatePublished - Nov 1 2015

    Keywords

    • Granulosa cells
    • Human ovary
    • Matrix metalloprotease
    • Neurotrophin

    ASJC Scopus subject areas

    • Endocrinology
    • Molecular Biology
    • Endocrinology, Diabetes and Metabolism

    Fingerprint Dive into the research topics of 'Pro-nerve growth factor in the ovary and human granulosa cells'. Together they form a unique fingerprint.

  • Cite this