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

. 2008 Nov;149(11):5811-21.

doi: 10.1210/en.2008-0575. Epub 2008 Jul 10.

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

Affiliations

Iain J Clarke et al. Endocrinology. 2008 Nov.

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.

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