Central and peripheral administration of human relaxin‐2 to adult male rats inhibits food intake

Abstract

Relaxin is a polypeptide hormone involved in pregnancy and lactation. It is mainly secreted by the corpus luteum and placenta, but is expressed in a number of other tissues, including heart and brain. Within the brain, relaxin is expressed in the olfactory and limbic systems, the cortex and the hypothalamic arcuate nucleus (ARC). Its cognate receptor, relaxin family peptide receptor 1 (RXFP1), is also widely expressed in the brain, including the hypothalamic ARC and paraventricular nucleus (PVN), areas important in appetite regulation. The aim of this study was to investigate whether relaxin influences food intake through central hypothalamic circuits. The human form of relaxin, human relaxin-2 (H2) was administered centrally and peripherally to male Wistar rats and food intake measured. Behaviour was also assessed. Intracerebroventricular (ICV) administration of H2 significantly decreased 1-h food intake in the early dark phase [2.95 ± 0.45 g (saline) vs. 0.95 ± 0.18 g (180 pmol H2), p < 0.001]. ICV administration of H2 decreased feeding behaviour and increased grooming and headdown behaviour. Intraparaventricular injections of H2 significantly decreased 1-h food intake in the early dark phase [3.13 ± 0.35 g (saline) vs. 1.35 ± 0.33 g (18 pmol H2), p < 0.01, 1.61 ± 0.31 g (180 pmol H2), p < 0.05 and 1.23 ± 0.32 g (540 pmol H2), p < 0.001]. Intraperitoneal (IP) administration of H2 significantly decreased 1-h food intake in the early dark phase [4.63 ± 0.46 g (vehicle) vs. 3.08 ± 0.15 g (66 nmol H2), p < 0.01, 3.00 ± 0.17 g (200 nmol H2), p < 0.01 and 2.26 ± 0.36 g (660 nmol H2), p < 0.001]. Central and peripheral administration of H2 reduces the food intake in rats. This effect may be mediated via the PVN and/or other brain regions.