Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis

Sabine Heger, Claudio Mastronardi, Gregory Dissen, Alejandro Lomniczi, Ricardo Cabrera, Christian L. Roth, Heike Jung, Francesco Galimi, Wolfgang Sippell, Sergio Ojeda

    Research output: Contribution to journalArticle

    66 Citations (Scopus)

    Abstract

    The initiation of mammalian puberty and the maintenance of female reproductive cycles are events controlled by hypothalamic neurons that secrete the decapeptide gonadotropin-releasing hormone (GnRH). GnRH secretion is, in turn, controlled by changes in neuronal and glial inputs to GnRH-producing neurons. The hierarchical control of the process is unknown, but it requires coordinated regulation of these cell-cell interactions. Here we report the functional characterization of a gene (termed enhanced at puberty 1 [EAP1]) that appears to act as an upstream transcriptional regulator of neuronal networks controlling female reproductive function. EAP1 expression increased selectively at puberty in both the nonhuman primate and rodent hypothalamus. EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity. Inhibition of EAP1 expression, targeted to the rodent hypothalamus via lentivirus-mediated delivery of EAP1 siRNAs, delayed puberty, disrupted estrous cyclicity, and resulted in ovarian abnormalities. These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function.

    Original languageEnglish (US)
    Pages (from-to)2145-2154
    Number of pages10
    JournalJournal of Clinical Investigation
    Volume117
    Issue number8
    DOIs
    StatePublished - Aug 1 2007

    Fingerprint

    Puberty
    Gonadotropin-Releasing Hormone
    Neurons
    Hypothalamus
    Rodentia
    RING Finger Domains
    Delayed Puberty
    Genes
    Lentivirus
    Periodicity
    Nuclear Proteins
    Cell Communication
    Neuroglia
    Primates
    Reproduction
    Maintenance
    Brain

    ASJC Scopus subject areas

    • Medicine(all)

    Cite this

    Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis. / Heger, Sabine; Mastronardi, Claudio; Dissen, Gregory; Lomniczi, Alejandro; Cabrera, Ricardo; Roth, Christian L.; Jung, Heike; Galimi, Francesco; Sippell, Wolfgang; Ojeda, Sergio.

    In: Journal of Clinical Investigation, Vol. 117, No. 8, 01.08.2007, p. 2145-2154.

    Research output: Contribution to journalArticle

    Heger, S, Mastronardi, C, Dissen, G, Lomniczi, A, Cabrera, R, Roth, CL, Jung, H, Galimi, F, Sippell, W & Ojeda, S 2007, 'Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis', Journal of Clinical Investigation, vol. 117, no. 8, pp. 2145-2154. https://doi.org/10.1172/JCI31752
    Heger, Sabine ; Mastronardi, Claudio ; Dissen, Gregory ; Lomniczi, Alejandro ; Cabrera, Ricardo ; Roth, Christian L. ; Jung, Heike ; Galimi, Francesco ; Sippell, Wolfgang ; Ojeda, Sergio. / Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 8. pp. 2145-2154.
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