Puberty is an essential developmental process for reproductive function and its initiation is tightly linked to nutritional status. Activation of the hypothalamic-pituitary-gonadal (HPG) drives pubertal onset by a surge in gonadotropin-releasing hormone (GnRH) activity, and thus
gonadotropin and sex steroid production. Galanin-like peptide (GALP) is a neuropeptide expressed by a discrete population of neurons in the hypothalamic arcuate nucleus with established roles in energy homeostasis and reproduction. GALP is regulated by metabolic signals and may provide a link between nutritional status and reproductive development. While reduced GALP activity is associated with delayed puberty, the effects of increased GALP activity remain unknown. This study aimed to elucidate the role of GALP in pubertal onset using neonatally food-restricted mice as a model of delayed puberty. GALP-Cre mice were crossed with hM3Dq-flox mice to generate offspring expressing the excitatory designer receptor (hM3Dq DREADD) specifically in GALP neurons. Mice were raised in small (6 pups) or large (12 pups) per litter, as previous studies demonstrated delayed puberty in larger litters. From weaning (~day 21), mice received clozapine-N-oxide (CNO) in drinking water (5 mg/kg/day) to chronically activate GALP neurons. Puberty onset was assessed by preputial separation in males and vaginal opening and first estrous in female mice. Neonatal food-restriction delayed puberty onset in non-GALP-activated males(p=.043), while GALP activation rescued this delay. GALP-activated males also reached puberty at a lower body weight (p<.001). In females, food-restriction did not affect vaginal opening but delayed first estrous in non-GALP activated mice (p=.018). Interestingly, GALP-activation delayed vaginal opening and first estrous (p<.001), while all female mice reached puberty at a similar body weight. These findings suggest that GALP-activation promotes pubertal development in
males, while delaying vaginal opening and first estrous in females, highlighting a sex-specific role for GALP in the regulation of pubertal timing