Rln3, also known as relaxin-3, is a neuropeptide belonging to the insulin-relaxin superfamily. It plays significant roles in multiple biological processes. RLN3-expressing neurons are mainly located in the nucleus incertus of the dorsal pons and project axons to the forebrain, including the hypothalamus. RLN3 is involved in the regulation of feeding behavior, stress response, and may also play a role in memory-related processes [1,2,3,4]. Genetic models, such as mouse models, are valuable for studying its functions.

In terms of feeding behavior, central administration of RLN3 in rats increases food intake, and in female rats, RLN3/RXFP3 signaling in the hypothalamic paraventricular nucleus is necessary for binge-eating behavior. RLN3 knockout female mice are hypoactive, and RLN3 produces stronger orexigenic and obesogenic effects in female rats compared to male rats [1,2]. Regarding the stress-response system, intracerebroventricular administration of RLN3 in rats can stimulate the hypothalamopituitary CRF-ACTH system during the acute response [4].

In conclusion, Rln3 is crucial for regulating feeding behavior and the stress-response system. Studies using gene knockout mouse models have revealed its sex-specific effects on food intake and body weight gain, as well as its role in binge-eating disorder, thus providing insights into potential therapeutic targets for eating disorders that are more prevalent in women [1,2].