Increased hypothalamic GPR54 signaling

A potential mechanism for initiation of puberty in primates

Muhammad Shahab, Claudio Mastronardi, Stephanie B. Seminara, William F. Crowley, Sergio Ojeda, Tony M. Plant

    Research output: Contribution to journalArticle

    642 Citations (Scopus)

    Abstract

    To further study the role of GPR54 signaling in the onset of primate puberty, we used the monkey to examine the ability of kisspeptin-10 to elicit the release of gonadotropin-releasing hormone (GnRH) precociously, and we describe the expression of GPR54 and KiSS-1 in the hypothalamus during the peripubertal period. Agonadal juvenile male monkeys were implanted with a lateral cerebroventricular cannula and a jugular vein catheter. The responsiveness of the juvenile pituitary to endogenous GnRH release was heightened with a chronic pulsatile i.v. infusion of synthetic GnRH before kisspeptin-10 (112-121) injection. Intracerebroventricular (30 μg or 100 μg) or i.v. (100 μg) bolus injections of kisspeptin-10 elicited a robust GnRM discharge, as reflected by luteinizing hormone secretion, which was abolished by pretreatment with a GnRH-receptor antagonist. RNA was isolated from the hypothalamus of agonadal males before (juvenile) and after (pubertal) the pubertal resurgence of pulsatile GnRH release and from juvenile, early pubertal, and midpubertal ovary-intact females. KiSS-1 mRNA levels detected by real-time PCR increased with puberty in both male and female monkeys. In intact females, but not in agonadal males, GPR54 mRNA levels in the hypothalamus increased ≈ 3-fold from the juvenile to midpubertal stage. Hybridization histochemistry indicated robust KiSS-1 and GPR54 mRNA expression in the region of the arcuate nucleus. These findings are consistent with the hypothesis that GPR54 signaling by its cognate ligand in the primate hypothalamus may be activated at the end of the juvenile phase of development and may contribute to the pubertal resurgence of pulsatile GnRH release, the central drive for puberty.

    Original languageEnglish (US)
    Pages (from-to)2129-2134
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume102
    Issue number6
    DOIs
    StatePublished - Feb 8 2005

    Fingerprint

    Puberty
    Gonadotropin-Releasing Hormone
    Primates
    Hypothalamus
    Haplorhini
    Messenger RNA
    LHRH Receptors
    Hormone Antagonists
    Arcuate Nucleus of Hypothalamus
    Injections
    Jugular Veins
    Luteinizing Hormone
    Real-Time Polymerase Chain Reaction
    Ovary
    Catheters
    RNA
    Ligands
    human KISS1 protein

    Keywords

    • Development
    • Gonadotropin-releasing hormone
    • GPR54
    • Hypothalamus
    • Kisspeptins
    • Monkey

    ASJC Scopus subject areas

    • Genetics
    • General

    Cite this

    Increased hypothalamic GPR54 signaling : A potential mechanism for initiation of puberty in primates. / Shahab, Muhammad; Mastronardi, Claudio; Seminara, Stephanie B.; Crowley, William F.; Ojeda, Sergio; Plant, Tony M.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 6, 08.02.2005, p. 2129-2134.

    Research output: Contribution to journalArticle

    Shahab, Muhammad ; Mastronardi, Claudio ; Seminara, Stephanie B. ; Crowley, William F. ; Ojeda, Sergio ; Plant, Tony M. / Increased hypothalamic GPR54 signaling : A potential mechanism for initiation of puberty in primates. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 6. pp. 2129-2134.
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