Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion

Iain J. Clarke, Ika P. Sari, Yue Qi, Jeremy T. Smith, Helena C. Parkington, Takayoshi Ubuka, Javed Iqbal, Qun Li, Alan Tilbrook, Kevin Morgan, Adam J. Pawson, Kazuyoshi Tsutsui, Robert P. Millar, George E. Bentley

    Research output: Contribution to journalArticle

    231 Citations (Scopus)

    Abstract

    We identified a gene in the ovine hypothalamus encoding for RFamide-related peptide-3 (RFRP-3), and tested the hypothesis that this system produces a hypophysiotropic hormone that inhibits the function of pituitary gonadotropes. The RFRP-3 gene encodes for a peptide that appears identical to human RFRP-3 homolog. Using an antiserum raised against RFRP-3, cells were localized to the dorsomedial hypothalamic nucleus/paraventricular nucleus of the ovine brain and shown to project to the neurosecretory zone of the ovine median eminence, predicating a role for this peptide in the regulation of anterior pituitary gland function. Ovine RFRP-3 peptide was tested for biological activity in vitro and in vivo, and was shown to reduce LH and FSH secretion in a specific manner. RFRP-3 potently inhibited GnRH-stimulated mobilization of intracellular calcium in gonadotropes. These data indicate that RFRP-3 is a specific and potent mammalian gonadotropin-inhibiting hormone, and that it acts upon pituitary gonadotropes to reduce GnRH-stimulated gonadotropin secretion.

    Original languageEnglish
    Pages (from-to)5811-5821
    Number of pages11
    JournalEndocrinology
    Volume149
    Issue number11
    DOIs
    Publication statusPublished - 2008 Nov

    Fingerprint

    Gonadotropins
    Sheep
    Gonadotropin-Releasing Hormone
    Peptides
    Dorsomedial Hypothalamic Nucleus
    Pituitary Hormone-Releasing Hormones
    Median Eminence
    Anterior Pituitary Gland
    Paraventricular Hypothalamic Nucleus
    RFamide peptide
    Genes
    Hypothalamus
    Immune Sera
    Hormones
    Calcium
    Brain

    ASJC Scopus subject areas

    • Endocrinology

    Cite this

    Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion. / Clarke, Iain J.; Sari, Ika P.; Qi, Yue; Smith, Jeremy T.; Parkington, Helena C.; Ubuka, Takayoshi; Iqbal, Javed; Li, Qun; Tilbrook, Alan; Morgan, Kevin; Pawson, Adam J.; Tsutsui, Kazuyoshi; Millar, Robert P.; Bentley, George E.

    In: Endocrinology, Vol. 149, No. 11, 11.2008, p. 5811-5821.

    Research output: Contribution to journalArticle

    Clarke, IJ, Sari, IP, Qi, Y, Smith, JT, Parkington, HC, Ubuka, T, Iqbal, J, Li, Q, Tilbrook, A, Morgan, K, Pawson, AJ, Tsutsui, K, Millar, RP & Bentley, GE 2008, 'Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion', Endocrinology, vol. 149, no. 11, pp. 5811-5821. https://doi.org/10.1210/en.2008-0575
    Clarke, Iain J. ; Sari, Ika P. ; Qi, Yue ; Smith, Jeremy T. ; Parkington, Helena C. ; Ubuka, Takayoshi ; Iqbal, Javed ; Li, Qun ; Tilbrook, Alan ; Morgan, Kevin ; Pawson, Adam J. ; Tsutsui, Kazuyoshi ; Millar, Robert P. ; Bentley, George E. / Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion. In: Endocrinology. 2008 ; Vol. 149, No. 11. pp. 5811-5821.
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