erbB-1 and erbB-4 receptors act in concert to facilitate female sexual development and mature reproductive function

Vincent Prevot, Alejandro Lomniczi, Gabriel Corfas, Sergio Ojeda

    Research output: Contribution to journalArticle

    57 Citations (Scopus)

    Abstract

    Glial erbB-1 and erbB-4 receptors are key components of the process by which neuroendocrine glial cells control LHRH secretion and the onset of female puberty. We now provide evidence that these two signaling systems work in a coordinated fashion to control reproductive function. To generate animals carrying functionally impaired erbB-1 and erbB-4 receptors, we crossed Waved 2 (Wa-2+/+) mice harboring a point mutation of the erbB-1 receptor with mice expressing a dominant-negative erbB-4 receptor in astrocytes. In comparison to single-deficient mice, double-mutant animals exhibited a further delay in the onset of puberty and a strikingly diminished adult reproductive capacity. Ligand-dependent erbB receptor phosphorylation and erbB-mediated MAPK (ERK 1/2) phosphorylation were impaired in mutant astrocytes. Wa-2+/+ or double-mutant astrocytes failed to respond to TGFα with production of prostaglandin E2, one of the factors mediating the stimulatory effect of astroglial erbB receptor activation on LHRH release. Medium conditioned by Wa-2+/+ or double-mutant astrocytes treated with TGFα failed to stimulate LHRH release from GT1-7 cells. The LH response to ovariectomy was significantly attenuated in mutant mice in comparison with wild-type controls. Although the Wa-2 mutation affects all cells bearing erbB-1 receptors, these results suggest that a major defect underlying the reproductive defects of animals with impaired erbB signaling is a decreased ability of glial cells to stimulate LHRH release. Thus, a coordinated involvement of erbB-1 and erbB-4 signaling systems is required for the normalcy of sexual development and the maintenance of mature female reproductive function.

    Original languageEnglish (US)
    Pages (from-to)1465-1472
    Number of pages8
    JournalEndocrinology
    Volume146
    Issue number3
    DOIs
    StatePublished - Mar 2005

    Fingerprint

    Sexual Development
    Gonadotropin-Releasing Hormone
    Astrocytes
    Neuroglia
    Puberty
    Epidermal Growth Factor Receptor
    Phosphorylation
    Neuroendocrine Cells
    Ovariectomy
    Conditioned Culture Medium
    Point Mutation
    Dinoprostone
    Maintenance
    Ligands
    Mutation
    ErbB-4 Receptor
    ErbB Receptors

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism

    Cite this

    erbB-1 and erbB-4 receptors act in concert to facilitate female sexual development and mature reproductive function. / Prevot, Vincent; Lomniczi, Alejandro; Corfas, Gabriel; Ojeda, Sergio.

    In: Endocrinology, Vol. 146, No. 3, 03.2005, p. 1465-1472.

    Research output: Contribution to journalArticle

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