Objective  To explore the effect of melatonin (MLT) on the initiation of puberty in female mice and on the expression level of phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in the hypothalamus.    Methods  Seventy-eight 20-day-old female KM mice were randomly divided into melatonin (MLT) group and normal saline (NS) group, with 39 mice in each group. Starting at 22 days of age, the MLT group was given a subcutaneous injection of 1mg/kg melatonin and the NS group was given an equal volume of saline. Thirty-two days of age were selected as the sampling point before puberty initiation and 13 mice were executed in each of the two groups, while 37 and 42 days of age were selected as the sampling point after puberty initiation and 13 mice were executed in each of the two groups. Observation of vaginal opening time in mice, weighing of ovaries and uterus to calculate organ indices. HE staining to observe the number of ovarian corpora lutea. The levels of serum luteinizing hormone（LH）were determined by ELISA. The mRNA and protein expression levels of PI3K/Akt/mTOR pathway in hypothalamus were detected by Real-time PCR and Western blotting.    Results  Compared with the normal saline group, mice in the melatonin group had significantly delayed vaginal opening time (P<0.05), decreased significantly ovarian and uterine volume and index (P<0.05), decreased significantly serum LH levels (P<0.05), and decreased significantly mRNA and protein expression levels of the hypothalamic PI3K/Akt/mTOR pathway(P<0.05).   Conclusion  Melatonin delays puberty initiation in mice by a mechanism that may be related to inhibition of the hypothalamic PI3K/Akt/mTOR signalling pathway. 

Melatonin, Puberty onset, Hypothalamic-pituitary-gonad axis, Phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway, Enzyme-linked immunosorbent assay, Mouse