Sex-Specific Effects of Chronic Administration of Relaxin-3 on Food Intake, Body Weight and the Hypothalamic-Pituitary-Gonadal Axis in Rats

The present study examined the effects of chronic central administration of relaxin‐3 (RLN3) on food intake, body weight and fat mass in intact and sterilised male and female rats, as well as on hypothalamic‐pituitary‐gonadal (HPG) axis activity in intact male and female rats that received i.c.v. infusions of RLN3 (400 pmol/day) or vehicle during a 14‐day period. The intact RLN3‐injected rats displayed a higher body weight than the vehicle‐treated groups, and this increase was statistically significantly stronger in female rats compared to male rats. In addition, feed efficiency and gonadal white adipose tissue weight were higher in female RLN3‐injected rats. Chronic i.c.v. administration of RLN3 activated the HPG axis in intact male rats, whereas inhibition of the HPG axis was observed in intact female rats. RLN3 significantly increased the plasma levels of luteinising hormone and follicular‐stimulating hormone in male rats but not in female rats. Conversely, hypothalamic expression of gonadotrophin‐releasing hormone mRNA was decreased by RLN3 in female rats but not in male rats. In addition, the plasma levels of oestradiol were significantly decreased by RLN3 administration in female rats. Consequently, intact RLN3‐injected female rats failed to display phasic inhibition of eating during oestrus. Sex‐specific effects of RLN3 on food intake and body weight were also observed in ovariectomised female and orchidectomised male rats, suggesting that the sex‐specific effects of RLN3 on energy metabolism are independent on the differential effects of RLN3 on HPG axis activity in male and female rats.