Glia-to-neuron signaling and the neuroendocrine control of female puberty

Sergio Ojeda, Y. J. Ma, B. J. Lee, V. Prevot, J. Veldhuis, S. Raff, W. Bremner, S. Kawashima, N. Kochupillai

    Research output: Contribution to journalArticle

    86 Citations (Scopus)

    Abstract

    It is becoming increasingly clear that astroglial cells are active participants in the process by which information is generated and disseminated within the central nervous system (CNS). In the hypothalamus, astrocytes regulate the secretory activity of neuroendocrine neurons. They contribute to facilitating sexual development by stimulating the release of luteinizing hormone-releasing hormone (LHRH), the neuropeptide that controls sexual development, from LHRH neurons. Astrocytes secrete several growth factors able to stimulate LHRH secretion. Two members of the epidermal growth factor (EGF) family - transforming growth factor alpha (TGFα) and the neuregulins (NRGs) - are produced in hypothalamic astrocytes and elicit LHRH secretion indirectly, via activation of receptor complexes formed by three members of the EGF receptor family, also located on astrocytes. Activation of these receptors results in the production of at least one neuroactive substance, prostaglandin E2 (PGE2), which stimulates LHRH secretion upon binding to specific receptors on LHRH neurons. Overexpression of TGFα in the hypothalamus accelerates puberty, whereas blockade of either TGFα or NRG actions delays the process, indicating that both peptides are physiological components of the neuroendocrine mechanism that controls sexual maturation. An increase in hypothalamic expression of at least two of the erbB receptors is initiated before the pubertal augmentation of gonadal steroid secretion and is completed on the day of the first preovulatory surge of gonadotropins. This secondary increase is brought about by gonadal steroids. Estrogen and progesterone facilitate erbB-mediated glia-to-LHRH neuron communication by enhancing astrocytic gene expression of at least one of the EGF-related ligands (TGFα) and two of the receptors (erbB-2 and erbB-4). They also facilitate the LHRH response to PGE2 via induction of PGE2 receptors in LHRH neurons. A search for genes that may act as upstream regulators of the pubertal process resulted in the identification of two potential candidates: Oct-2, a POU domain gene originally described in cells of the immune system, and TTF-1, a member of the Nkx family of homeodomain transcriptional regulators required for diencephalic morphogenesis. The hypothalamic expression of both genes increases during juvenile development before the first hormonal manifestations of puberty take place. Their mRNA transcripts are localized to specific hypothalamic cellular subsets, where they appear to regulate different, but interactive, components of the neuronal-glial complex controlling LHRH secretion. While Oct-2 transactivates the TGFα promoter, TTF-1 does so to the erbB-2 and LHRH genes but inhibits preproenkephalin promoter activity, suggesting that both transcriptional regulators may act coordinately in the normal hypothalamus to activate genes involved in facilitating the advent of puberty and repress those restraining sexual development. Altogether, these observations indicate that the central activation of the pubertal process involves the participation of both neuronal and astroglial networks and the contribution of upstream transcriptional regulators acting on both the neuronal and glial components of the system.

    Original languageEnglish (US)
    Pages (from-to)197-224
    Number of pages28
    JournalRecent Progress in Hormone Research
    Volume55
    StatePublished - 2000

    Fingerprint

    Puberty
    Gonadotropin-Releasing Hormone
    Neuroglia
    Neurons
    Transforming Growth Factor alpha
    Astrocytes
    Sexual Development
    Neuregulins
    Dinoprostone
    Hypothalamus
    Epidermal Growth Factor Receptor
    Genes
    Steroids
    Prostaglandin Receptors
    LHRH Receptors
    Gene Expression
    Sexual Maturation
    Neuropeptides
    Gonadotropins
    Morphogenesis

    ASJC Scopus subject areas

    • Endocrinology

    Cite this

    Ojeda, S., Ma, Y. J., Lee, B. J., Prevot, V., Veldhuis, J., Raff, S., ... Kochupillai, N. (2000). Glia-to-neuron signaling and the neuroendocrine control of female puberty. Recent Progress in Hormone Research, 55, 197-224.

    Glia-to-neuron signaling and the neuroendocrine control of female puberty. / Ojeda, Sergio; Ma, Y. J.; Lee, B. J.; Prevot, V.; Veldhuis, J.; Raff, S.; Bremner, W.; Kawashima, S.; Kochupillai, N.

    In: Recent Progress in Hormone Research, Vol. 55, 2000, p. 197-224.

    Research output: Contribution to journalArticle

    Ojeda, S, Ma, YJ, Lee, BJ, Prevot, V, Veldhuis, J, Raff, S, Bremner, W, Kawashima, S & Kochupillai, N 2000, 'Glia-to-neuron signaling and the neuroendocrine control of female puberty', Recent Progress in Hormone Research, vol. 55, pp. 197-224.
    Ojeda, Sergio ; Ma, Y. J. ; Lee, B. J. ; Prevot, V. ; Veldhuis, J. ; Raff, S. ; Bremner, W. ; Kawashima, S. ; Kochupillai, N. / Glia-to-neuron signaling and the neuroendocrine control of female puberty. In: Recent Progress in Hormone Research. 2000 ; Vol. 55. pp. 197-224.
    @article{c3202c9a73a84430ad65f485b7ccaa46,
    title = "Glia-to-neuron signaling and the neuroendocrine control of female puberty",
    abstract = "It is becoming increasingly clear that astroglial cells are active participants in the process by which information is generated and disseminated within the central nervous system (CNS). In the hypothalamus, astrocytes regulate the secretory activity of neuroendocrine neurons. They contribute to facilitating sexual development by stimulating the release of luteinizing hormone-releasing hormone (LHRH), the neuropeptide that controls sexual development, from LHRH neurons. Astrocytes secrete several growth factors able to stimulate LHRH secretion. Two members of the epidermal growth factor (EGF) family - transforming growth factor alpha (TGFα) and the neuregulins (NRGs) - are produced in hypothalamic astrocytes and elicit LHRH secretion indirectly, via activation of receptor complexes formed by three members of the EGF receptor family, also located on astrocytes. Activation of these receptors results in the production of at least one neuroactive substance, prostaglandin E2 (PGE2), which stimulates LHRH secretion upon binding to specific receptors on LHRH neurons. Overexpression of TGFα in the hypothalamus accelerates puberty, whereas blockade of either TGFα or NRG actions delays the process, indicating that both peptides are physiological components of the neuroendocrine mechanism that controls sexual maturation. An increase in hypothalamic expression of at least two of the erbB receptors is initiated before the pubertal augmentation of gonadal steroid secretion and is completed on the day of the first preovulatory surge of gonadotropins. This secondary increase is brought about by gonadal steroids. Estrogen and progesterone facilitate erbB-mediated glia-to-LHRH neuron communication by enhancing astrocytic gene expression of at least one of the EGF-related ligands (TGFα) and two of the receptors (erbB-2 and erbB-4). They also facilitate the LHRH response to PGE2 via induction of PGE2 receptors in LHRH neurons. A search for genes that may act as upstream regulators of the pubertal process resulted in the identification of two potential candidates: Oct-2, a POU domain gene originally described in cells of the immune system, and TTF-1, a member of the Nkx family of homeodomain transcriptional regulators required for diencephalic morphogenesis. The hypothalamic expression of both genes increases during juvenile development before the first hormonal manifestations of puberty take place. Their mRNA transcripts are localized to specific hypothalamic cellular subsets, where they appear to regulate different, but interactive, components of the neuronal-glial complex controlling LHRH secretion. While Oct-2 transactivates the TGFα promoter, TTF-1 does so to the erbB-2 and LHRH genes but inhibits preproenkephalin promoter activity, suggesting that both transcriptional regulators may act coordinately in the normal hypothalamus to activate genes involved in facilitating the advent of puberty and repress those restraining sexual development. Altogether, these observations indicate that the central activation of the pubertal process involves the participation of both neuronal and astroglial networks and the contribution of upstream transcriptional regulators acting on both the neuronal and glial components of the system.",
    author = "Sergio Ojeda and Ma, {Y. J.} and Lee, {B. J.} and V. Prevot and J. Veldhuis and S. Raff and W. Bremner and S. Kawashima and N. Kochupillai",
    year = "2000",
    language = "English (US)",
    volume = "55",
    pages = "197--224",
    journal = "Recent Progress in Hormone Research",
    issn = "0079-9963",
    publisher = "The Endocrine Society",

    }

    TY - JOUR

    T1 - Glia-to-neuron signaling and the neuroendocrine control of female puberty

    AU - Ojeda, Sergio

    AU - Ma, Y. J.

    AU - Lee, B. J.

    AU - Prevot, V.

    AU - Veldhuis, J.

    AU - Raff, S.

    AU - Bremner, W.

    AU - Kawashima, S.

    AU - Kochupillai, N.

    PY - 2000

    Y1 - 2000

    N2 - It is becoming increasingly clear that astroglial cells are active participants in the process by which information is generated and disseminated within the central nervous system (CNS). In the hypothalamus, astrocytes regulate the secretory activity of neuroendocrine neurons. They contribute to facilitating sexual development by stimulating the release of luteinizing hormone-releasing hormone (LHRH), the neuropeptide that controls sexual development, from LHRH neurons. Astrocytes secrete several growth factors able to stimulate LHRH secretion. Two members of the epidermal growth factor (EGF) family - transforming growth factor alpha (TGFα) and the neuregulins (NRGs) - are produced in hypothalamic astrocytes and elicit LHRH secretion indirectly, via activation of receptor complexes formed by three members of the EGF receptor family, also located on astrocytes. Activation of these receptors results in the production of at least one neuroactive substance, prostaglandin E2 (PGE2), which stimulates LHRH secretion upon binding to specific receptors on LHRH neurons. Overexpression of TGFα in the hypothalamus accelerates puberty, whereas blockade of either TGFα or NRG actions delays the process, indicating that both peptides are physiological components of the neuroendocrine mechanism that controls sexual maturation. An increase in hypothalamic expression of at least two of the erbB receptors is initiated before the pubertal augmentation of gonadal steroid secretion and is completed on the day of the first preovulatory surge of gonadotropins. This secondary increase is brought about by gonadal steroids. Estrogen and progesterone facilitate erbB-mediated glia-to-LHRH neuron communication by enhancing astrocytic gene expression of at least one of the EGF-related ligands (TGFα) and two of the receptors (erbB-2 and erbB-4). They also facilitate the LHRH response to PGE2 via induction of PGE2 receptors in LHRH neurons. A search for genes that may act as upstream regulators of the pubertal process resulted in the identification of two potential candidates: Oct-2, a POU domain gene originally described in cells of the immune system, and TTF-1, a member of the Nkx family of homeodomain transcriptional regulators required for diencephalic morphogenesis. The hypothalamic expression of both genes increases during juvenile development before the first hormonal manifestations of puberty take place. Their mRNA transcripts are localized to specific hypothalamic cellular subsets, where they appear to regulate different, but interactive, components of the neuronal-glial complex controlling LHRH secretion. While Oct-2 transactivates the TGFα promoter, TTF-1 does so to the erbB-2 and LHRH genes but inhibits preproenkephalin promoter activity, suggesting that both transcriptional regulators may act coordinately in the normal hypothalamus to activate genes involved in facilitating the advent of puberty and repress those restraining sexual development. Altogether, these observations indicate that the central activation of the pubertal process involves the participation of both neuronal and astroglial networks and the contribution of upstream transcriptional regulators acting on both the neuronal and glial components of the system.

    AB - It is becoming increasingly clear that astroglial cells are active participants in the process by which information is generated and disseminated within the central nervous system (CNS). In the hypothalamus, astrocytes regulate the secretory activity of neuroendocrine neurons. They contribute to facilitating sexual development by stimulating the release of luteinizing hormone-releasing hormone (LHRH), the neuropeptide that controls sexual development, from LHRH neurons. Astrocytes secrete several growth factors able to stimulate LHRH secretion. Two members of the epidermal growth factor (EGF) family - transforming growth factor alpha (TGFα) and the neuregulins (NRGs) - are produced in hypothalamic astrocytes and elicit LHRH secretion indirectly, via activation of receptor complexes formed by three members of the EGF receptor family, also located on astrocytes. Activation of these receptors results in the production of at least one neuroactive substance, prostaglandin E2 (PGE2), which stimulates LHRH secretion upon binding to specific receptors on LHRH neurons. Overexpression of TGFα in the hypothalamus accelerates puberty, whereas blockade of either TGFα or NRG actions delays the process, indicating that both peptides are physiological components of the neuroendocrine mechanism that controls sexual maturation. An increase in hypothalamic expression of at least two of the erbB receptors is initiated before the pubertal augmentation of gonadal steroid secretion and is completed on the day of the first preovulatory surge of gonadotropins. This secondary increase is brought about by gonadal steroids. Estrogen and progesterone facilitate erbB-mediated glia-to-LHRH neuron communication by enhancing astrocytic gene expression of at least one of the EGF-related ligands (TGFα) and two of the receptors (erbB-2 and erbB-4). They also facilitate the LHRH response to PGE2 via induction of PGE2 receptors in LHRH neurons. A search for genes that may act as upstream regulators of the pubertal process resulted in the identification of two potential candidates: Oct-2, a POU domain gene originally described in cells of the immune system, and TTF-1, a member of the Nkx family of homeodomain transcriptional regulators required for diencephalic morphogenesis. The hypothalamic expression of both genes increases during juvenile development before the first hormonal manifestations of puberty take place. Their mRNA transcripts are localized to specific hypothalamic cellular subsets, where they appear to regulate different, but interactive, components of the neuronal-glial complex controlling LHRH secretion. While Oct-2 transactivates the TGFα promoter, TTF-1 does so to the erbB-2 and LHRH genes but inhibits preproenkephalin promoter activity, suggesting that both transcriptional regulators may act coordinately in the normal hypothalamus to activate genes involved in facilitating the advent of puberty and repress those restraining sexual development. Altogether, these observations indicate that the central activation of the pubertal process involves the participation of both neuronal and astroglial networks and the contribution of upstream transcriptional regulators acting on both the neuronal and glial components of the system.

    UR - http://www.scopus.com/inward/record.url?scp=0034500251&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0034500251&partnerID=8YFLogxK

    M3 - Article

    C2 - 11036938

    AN - SCOPUS:0034500251

    VL - 55

    SP - 197

    EP - 224

    JO - Recent Progress in Hormone Research

    JF - Recent Progress in Hormone Research

    SN - 0079-9963

    ER -