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J Physiol Volume 573, Number 1, 237-249, May 15, 2006 DOI: 10.1113/jphysiol.2006.106856
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INTEGRATIVE

Novel role of 26RFa, a hypothalamic RFamide orexigenic peptide, as putative regulator of the gonadotropic axis

V. M. Navarro1, R. Fernández-Fernández1, R. Nogueiras2, E. Vigo1, S. Tovar2, N. Chartrel3, O. Le Marec3, J. Leprince3, E. Aguilar1, L. Pinilla1, C. Dieguez2, H. Vaudry3 and M. Tena-Sempere1

1 Department of Cell Biology, Physiology and Immunology, University of Córdoba, 14004 Córdoba, Spain
2 Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
3 Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide research (IFRMP 23), INSERM U 413, University of Rouen, 76821 Mont-Saint-Aignan, France

The close link between reproductive function and body energy stores relies on a complex neuroendocrine network of common regulatory signals, the nature of which is yet to be fully elucidated. Recently, 26RFa was identified in amphibians and mammals as a conserved hypothalamic neuropeptide of the RFamide family, with a potent orexigenic activity. Yet, despite its proposed role as hypophysiotropic factor, the function of 26RFa in the control of pituitary gonadotropins and, hence, of the reproductive axis remains unexplored. In the present study, the effects of 26RFa on gonadotropin secretion were evaluated in the rat by a combination of in vitro and in vivo approaches. At the pituitary, 26RFa dose-dependently enhanced basal and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion from male and cyclic female rats. This effect was mimicked by the active fragment 26RFa20–26, as well as by the related 43RFa peptide. Moreover, expression of the genes encoding 26RFa and its putative receptor, GPR103, was demonstrated in rat pituitary throughout postnatal development. In vivo, intracerebral injection of 26RFa evoked a significant increase in serum LH levels in cyclic and ovariectomized females; this response which was also observed after central injection of 26RFa20–26 and 43RFa peptides, as well as after systemic administration of 26RFa. Conversely, central and systemic injection of 26RFa failed to significantly modify gonadotropin secretion in adult male rats, even after repeated administration of the peptide. In summary, we present herein novel evidence for the potential role of the orexigenic peptide 26RFa in the control of the gonadotropic axis, thus suggesting its potential involvement in the joint control of energy balance and reproduction, especially in the female.

(Received 2 February 2006; accepted after revision 10 March 2006; first published online 16 March 2006)
Corresponding author M. Tena-Sempere: Physiology Section, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, University of Córdoba, Avda. Menéndez Pidal s/n 14004, Córdoba, Spain. Email: fi1tesem{at}uco.es


V. M. Navarro and R. Fernández-Fernández contributed equally to this work.




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