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M Murakami, Obstetrics and Gynecology, Health Biosciences,The University of Tokushima, Tokushima, 770-8503, Japan
T Matsuzaki, Obstetrics and Gynecology, Health Biosciences,The University of Tokushima, Tokushima, Japan
T Iwasa, Obstetrics and Gynecology, Health Biosciences,The University of Tokushima, Tokushima, Japan
T Yasui, Obstetrics and Gynecology, Health Biosciences,The University of Tokushima, Tokushima, Japan
M Irahara, Obstetrics and Gynecology, Health Biosciences,The University of Tokushima, Tokushima, Japan
T Osugi, Biology, Waseda University, Tokyo, Japan
K Tsutsui, Biology, Waseda University, Tokyo, Japan

Correspondence: Masahiro Murakami, Email: mipu26{at}clin.med.tokushima-u.ac.jp

Abstract

Gonadotrophin-inhibitory hormone (GnIH), a newly discovered hypothalamic RFamide peptide, inhibits reproductive activity by decreasing gonadotrophin synthesis and release in birds. The gene of the mammalian RFamide-related peptides (RFRPs) is orthologous to the GnIH gene. This RFRP gene gives rise to the two biologically active peptides RFRP-1 and RFRP-3, and intracerebroventricular (i.c.v.) injections of RFRP-3 suppress luteinizing hormone (LH) secretion in several mammalian species. In this study, we show whether RFRP-3 affects LH secretion at the pituitary level and/or via the release of gonadotrophin-releasing hormone (GnRH) at the hypothalamus in mammals. To investigate the suppressive effects of RFRP-3 on the mean level of LH secretion and the frequency of pulsatile LH secretion in vivo, ovariectomized (OVX) mature rats were administered RFRP-3 using either i.c.v. or intravenous (i.v.) injections. Furthermore, the effect of RFRP-3 on LH secretion was also investigated using cultured female rat pituitary cells. With i.v. administrations, RFRP-3 significantly reduced plasma LH concentrations as compared to the physiological saline group. However, after i.c.v. RFRP-3 injections, neither the mean level of LH concentrations nor the frequency of the pulsatile LH secretion were affected. When using cultured pituitary cells, in the absence of GnRH, the suppressive effect of RFRP-3 on LH secretion was not clear, but when GnRH was present, RFRP-3 significantly suppressed LH secretion. These results suggest that RFRP-3 does not affect LH secretion via the release of GnRH, and that RFRP-3 directly acts upon the pituitary to suppress GnRH-stimulated LH secretion in female rats.

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