Intracerebroventricular injection of RFRP-3 delays puberty onset and stimulates growth hormone secretion in female rats

Background: Puberty onset is a complex, organized biological process with multilevel regulation, and its physiopathological mechanisms are yet to be elucidated. RFRP-3, the mammalian ortholog to gonadotropin-inhibitory hormone, is implicated in inhibiting the synthesis and release of gonadotropin in mammals. However, it is unclear whether RFRP-3 participates in regulating pubertal development. Methods: This study investigated the functional significance and regulatory mechanism of hypothalamic RFRP-3 neuropeptide in the onset of puberty in young female rats. On postnatal day 22, we implanted cannulas into the lateral ventricles of female rat pups. From postnatal day 28 to postnatal day 36, the intracerebroventricular injection of RFRP-3, or vehicle, was conducted twice a day. To investigate whether puberty onset was affected, we examined the body weight, age of vaginal opening, serum hormone levels, uterus and ovary development, and hypothalamic Kiss-1 mRNA expression. Results: Intracerebroventricular injection of RFRP-3 significantly decreased the serum concentrations of luteinizing hormone and estradiol, delayed uterine maturation, and postponed the time of vaginal opening. This study suggests that RFRP-3 can delay the onset of puberty in young female rats; the expression of Kiss-1 mRNA is potently inhibited in the RFRP-3 group. Moreover, our data show that RFRP-3 elevates serum growth hormone levels. Conclusions: These data suggest that intracerebroventricular injection of RFRP-3 significantly delays the onset of puberty in female rats. Additionally, RFRP-3 may be associated with prepubertal rise in the secretion of growth hormone.