Role of kisspeptin/GPR54 signaling pathways in prompting formation of precocious puberty

AIM: To explore the role of kisspeptin/GPR54 signaling pathway in the pathogenesis of precocious puberty based on female precocious puberty rat model induced by the single dose of danazol. METHODS: Female SD rats aged 3 d were randomly divided into normal group, vehicle group and model group. On the 5th day, the model rats were given a single subcutaneous injection of danazol with ethanol and ethylene glycol mixture. All rats were executed on 15 d, 25 d, 30 d, 35 d and 40 d, and the samples were collected to observe the sexual organ development. The levels of E₂, FSH and LH in peripheral blood were measured by ELISA. The Kiss-1 mRNA expression of Kiss-1, GPR54 and GnRH in hypothalamus was detected by real-time PCR. The kisspeptin expression in rat hypothalamus was observed by immunofluorescence. RESULTS: The time for puberty onset and sexual maturation in the model rats was significantly earlier than that in normal group and vehicle group. On days 25 and 30, the levels of peripheral sex hormones and uterine coefficients in model group were significantly higher than those in normal group and vehicle group. On days 25 and 30, the ovarian morphological development in the model rats was significantly earlier than that in normal group. On day 25, the mRNA expression of hypothalamic Kiss-1 and GnRH, and kisspeptin expression of hypothalamic arcuate nucleus in the model rats significantly increased compared with normal group and vehicle group. On day 30, kisspeptin expression of hypothalamic arcuate nucleus in the model rats decreased compared with normal group and vehicle group. On day 35, the mRNA expression of Kiss-1 and GnRH in the model rats decreased compared with normal group and vehicle group. The mRNA expression of GPR54 had no obvious difference among all groups. CONCLUSION: The Kiss-1 mRNA and kisspeptin expression in the model rats with precocious puberty is significantly increased in the hypothalamus during onset of puberty, suggesting that kisspeptin is an initiating factor for precocious puberty. Kisspeptin/GPR54 signaling pathway may play an important role in the occurrence of precocious puberty.