Gene networks and the neuroendocrine regulation of puberty

Sergio R. Ojeda, Christopher Dubay, Alejandro Lomniczi, Gabi Kaidar, Valerie Matagne, Ursula S. Sandau, Gregory A. Dissen

    Research output: Contribution to journalReview article

    109 Scopus citations

    Abstract

    A sustained increase in pulsatile release of gonadotrophin releasing hormone (GnRH) from the hypothalamus is an essential, final event that defines the initiation of mammalian puberty. This increase depends on coordinated changes in transsynaptic and glial-neuronal communication, consisting of activating neuronal and glial excitatory inputs to the GnRH neuronal network and the loss of transsynaptic inhibitory tone. It is now clear that the prevalent excitatory systems stimulating GnRH secretion involve a neuronal component consisting of excitatory amino acids (glutamate) and at least one peptide (kisspeptin), and a glial component that uses growth factors and small molecules for cell-cell signaling. GABAergic and opiatergic neurons provide transsynaptic inhibitory control to the system, but GABA neurons also exert direct excitatory effects on GnRH neurons. The molecular mechanisms that provide encompassing coordination to this cellular network are not known, but they appear to involve a host of functionally related genes hierarchically arranged. We envision that, as observed in other gene networks, the highest level of control in this network is provided by transcriptional regulators that, by directing expression of key subordinate genes, impose an integrative level of coordination to the neuronal and glial subsets involved in initiating the pubertal process. The use of high-throughput and gene manipulation approaches coupled to systems biology strategies should provide not only the experimental bases supporting this concept, but also unveil the existence of crucial components of network control not yet identified.

    Original languageEnglish (US)
    Pages (from-to)3-11
    Number of pages9
    JournalMolecular and Cellular Endocrinology
    Volume324
    Issue number1-2
    DOIs
    StatePublished - Aug 2010

    Keywords

    • Glial-neuronal communication
    • GnRH neurons
    • Hypothalamus
    • Timing of puberty
    • Transcriptional regulation

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Endocrinology

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