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

Iain James Clarke, Ika Puspita Sari, Yue Qi, Jeremy Troy Smith, Helena Cecilia Parkington, Takayoshi Ubuka, Javed Iqbal, Qun Li, Alan John Tilbrook, Kevin Morgan, Adam J Pawson, Kazuyoshi Tsutsui, Robert Millar, George Edward Bentley

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Abstract

We identified a gene in the ovine hypothalamus encoding for RFRP-3 and tested the hypothesis that this system produces an hypophysiotropic hormone which inhibits the function of pituitary gonadotropes. The RFRP-3 gene encodes for a peptide that appears identical to human RFRP-3 homologue. Using an antiserum raised against RFRP-3, cells were localised 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 mobilisation 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
Publication statusPublished - 2008

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