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Metabolic and neuroendocrine responses to RXFP3 modulation in the central nervous system

conference contribution
posted on 2009-04-01, 00:00 authored by S W Sutton, J Shelton, Craig SmithCraig Smith, J Williams, S Yun, T Motley, C Kuei, P Bonaventure, A Gundlach, C Liu, T Lovenberg
Neuroanatomical studies have shown relaxin-3 neurons, primarily found in the rodent nucleus incertus (NI), project widely into a large number of areas expressing the relaxin-3 receptor (RXFP3), and these data suggest relaxin-3/RXFP3 signaling modulates sensory, emotional, and neuroendocrine processing. The similar distribution of this receptor-ligand pair in the rat, mouse, and monkey brain suggests that experimental findings obtained in lower species will translate to higher species. A role for relaxin-3 and RXFP3 in modulating stress responses is strongly suggested by the expression of corticotropin-releasing factor R1 (CRF-R1) by NI cells, increased relaxin-3 expression in the NI after stress or CRF injection, and hormonal responses to intracerebroventricular (i.c.v.) relaxin-3 injection. Recent data are consistent with a further role for this ligand-receptor pair in modulating memory. In addition, relaxin-3 has been reported to modulate feeding and body weight control. Acute or chronic central (i.c.v. or intraparaventricular) injections of relaxin-3 have shown a consistent stimulatory effect on food consumption while relaxin was inactive, suggesting the phagic effect of relaxin-3 is mediated by RXFP3. We have confirmed the role of RXFP3 in modulating feeding and body weight by using a selective RXFP3 agonist (R3/I5) and antagonist [R3(Delta23-27)R/I5], collecting feeding, body weight, hormone, and body composition data. In addition, we have preliminary body weight and magnetic resonance imaging data from relaxin-3 knockout mice, which on a 129S5:B6 background are smaller and leaner than congenic controls. These data suggest relaxin-3, acting through RXFP3, is involved in coordinating stress, learning and memory, and feeding responses as predicted on the basis of neuroanatomy.

History

Event

International conference on relaxin and related peptides. Conference (5th : 2008 : Maui, Hawaii)

Volume

1160

Series

International conference on relaxin and related peptides

Pagination

242 - 249

Publisher

Wiley

Location

Maui, Hawaii

Place of publication

Medford, Mass.

Start date

2008-05-18

End date

2008-05-23

ISSN

0077-8923

eISSN

1749-6632

ISBN-13

9781573317214

Language

eng

Publication classification

E1.1 Full written paper - refereed

Copyright notice

2009, New York Academy of Sciences

Editor/Contributor(s)

G Bryant-Greenwood, C Bagnell, R Bathgate, O Sherwood

Title of proceedings

Proceedings of the International Conference on Relaxin and Related Peptides 2008