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Am J Physiol Endocrinol Metab 295: E278-E286, 2008. First published May 20, 2008; doi:10.1152/ajpendo.00028.2008
0193-1849/08 $8.00
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Relaxin-3 stimulates the hypothalamic-pituitary-gonadal axis

B. M. McGowan, S. A. Stanley, J. Donovan, E. L. Thompson, M. Patterson, N. M. Semjonous, J. V. Gardiner, K. G. Murphy, M. A. Ghatei, and S. R. Bloom

Division of Investigative Science, Department of Investigative Medicine, Imperial College London, London, United Kingdom

Submitted 16 January 2008 ; accepted in final form 13 May 2008

The hypothalamus plays a key role in the regulation of both energy homeostasis and reproduction. Evidence suggests that relaxin-3, a recently discovered member of the insulin superfamily, is an orexigenic hypothalamic neuropeptide. Relaxin-3 is thought to act in the brain via the RXFP3 receptor, although the RXFP1 receptor may also play a role. Relaxin-3, RXFP3, and RXFP1 are present in the hypothalamic paraventricular nucleus, an area with a well-characterized role in the regulation of energy balance that also modulates reproductive function by providing inputs to hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Other members of the relaxin family are known to play a role in the regulation of reproduction. However, the effects of relaxin-3 on reproductive function are unknown. We studied the role of relaxin-3 in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. Intracerebroventricular (5 nmol) and intraparaventricular (540–1,620 pmol) administration of human relaxin-3 (H3) in adult male Wistar rats significantly increased plasma luteinizing hormone (LH) 30 min postinjection. This effect was blocked by pretreatment with a peripheral GnRH antagonist. Central administration of human relaxin-2 showed no significant effect on plasma LH. H3 dose-dependently stimulated the release of GnRH from hypothalamic explants and GT1-7 cells, which express RXFP1 and RXFP3, but did not influence LH or follicle-stimulating hormone release from pituitary fragments in vitro. We have demonstrated a novel role for relaxin-3 in the stimulation of the HPG axis, putatively via hypothalamic GnRH neurons. Relaxin-3 may act as a central signal linking nutritional status and reproductive function.

RXFP3; RXFP1; paraventricular nucleus; gonadotropin-releasing hormone; gonadotropins


Address for reprint requests and other correspondence: S. R. Bloom, Dept. of Investigative Medicine, Division of Investigative Science, Imperial College London, 6th Floor Commonwealth Bldg., Hammersmith Campus, Du Cane Road, London W12 ONN, UK (e-mail: s.bloom{at}imperial.ac.uk)






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