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

    研究成果: Article査読

    247 被引用数 (Scopus)

    抄録

    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.

    本文言語English
    ページ(範囲)5811-5821
    ページ数11
    ジャーナルEndocrinology
    149
    11
    DOI
    出版ステータスPublished - 2008 11

    ASJC Scopus subject areas

    • Endocrinology

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