A role for TrkA nerve growth factor receptors in mammalian ovulation

Gregory Dissen, Diane F. Hill, Maria E. Costa, W. Les Dees, Hernan E. Lara, Sergio Ojeda

    Research output: Contribution to journalArticle

    120 Citations (Scopus)

    Abstract

    Several members of the neurotrophin (NT) family, including nerve growth factor (NGF), NT-3, and NT-4/5, are expressed in the mammalian ovary. As their respective receptor tyrosine kinases are also found in the gland, the possibility exists that NTs act directly on the gonads to exert effects unrelated to their support of the ovarian innervation. We now report that trkA, the NGF receptor tyrosine kinase, is involved in the acute activational process that leads to the first ovulation. The trkA gene becomes transiently expressed in periovulatory follicles at the time of the first preovulatory surge of gonadotropins at puberty; the increase in trkA messenger RNA (mRNA) con tent is dramatic (>100-fold), but transient (~9 h). No such changes in trkB or trkC mRNA were observed; the abundance of these mRNAs, which encode the receptor tyrosine kinases for NT-4/5 and brain-derived neurotrophic factor, and NT-3, respectively, remained at very low levels throughout puberty. In vivo and in vitro experiments demonstrated that the activation of trkA gene expression is brought about by the proestrous discharge of LH. The increase in trkA mRNA levels is mainly localized to cells of the follicular wall and interstitial tissue of the ovary. NGF mRNA abundance also increases at proestrus, with peak values detected about 5 h before ovulation; as in the case of trkA mRNA, NGF mRNA was found in thecal-interstitial cells. Both trkA and NGF protein, detected by immunohistochemistry, were localized to this same ovarian compartment. Interleukin-1β (IL-1β), a putative mediator of LH action, enhances both trkA and NGF gene expression in ovarian cells, an effect prevented by IL-1ra, a natural IL-1β receptor antagonist. IL-1β also stimulates PGE2 release, and this effect was inhibited by both NGF antibodies and a trk receptor blocker; NGF antibodies administered in vivo attenuated the increase in ovarian PGE2 synthesis that antedates ovulation. Immunoneutralization of NGF action or pharmacological blockade of trk tyrosine kinase activity targeted to one ovary resulted in the ipsilateral inhibition of ovulation. The remarkably narrow time frame of trkA gene activation at the completion of follicular growth suggests that NGF acting as a neuroendocrinotrophic factor in a developmentally restricted manner contributes to the acute cytodifferentiation process that leads to the first ovulation in mammals.

    Original languageEnglish (US)
    Pages (from-to)198-209
    Number of pages12
    JournalEndocrinology
    Volume137
    Issue number1
    DOIs
    StatePublished - 1996

    Fingerprint

    Nerve Growth Factor Receptors
    Nerve Growth Factor
    Ovulation
    Messenger RNA
    Neurotrophin 3
    Ovary
    Receptor Protein-Tyrosine Kinases
    Puberty
    Interleukin-1
    Dinoprostone
    Protein-Tyrosine Kinases
    Ovulation Inhibition
    Interleukin 1 Receptor Antagonist Protein
    Gene Expression
    Nerve Growth Factor Receptor
    Proestrus
    Interleukin-1 Receptors
    Antibodies
    Brain-Derived Neurotrophic Factor
    Nerve Growth Factors

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Dissen, G., Hill, D. F., Costa, M. E., Les Dees, W., Lara, H. E., & Ojeda, S. (1996). A role for TrkA nerve growth factor receptors in mammalian ovulation. Endocrinology, 137(1), 198-209. https://doi.org/10.1210/en.137.1.198

    A role for TrkA nerve growth factor receptors in mammalian ovulation. / Dissen, Gregory; Hill, Diane F.; Costa, Maria E.; Les Dees, W.; Lara, Hernan E.; Ojeda, Sergio.

    In: Endocrinology, Vol. 137, No. 1, 1996, p. 198-209.

    Research output: Contribution to journalArticle

    Dissen, G, Hill, DF, Costa, ME, Les Dees, W, Lara, HE & Ojeda, S 1996, 'A role for TrkA nerve growth factor receptors in mammalian ovulation', Endocrinology, vol. 137, no. 1, pp. 198-209. https://doi.org/10.1210/en.137.1.198
    Dissen, Gregory ; Hill, Diane F. ; Costa, Maria E. ; Les Dees, W. ; Lara, Hernan E. ; Ojeda, Sergio. / A role for TrkA nerve growth factor receptors in mammalian ovulation. In: Endocrinology. 1996 ; Vol. 137, No. 1. pp. 198-209.
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