Kiss1 Gene Expression and the Effects of Kisspeptin During Pubertal Development in the Ewe Lamb

Increased pulsatile release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) is critical for pubertal initiation of ovarian cycles in female mammals. Kisspeptin, a peptide product of the Kiss1 gene, is required for normal puberty. In Experiment 1, ovariectomized ewe lambs bearing subcutaneous estradiol implants were used to investigate Kiss1 gene expression in the preoptic area (POA) and hypothalamus during pubertal maturation of the reproductive neuroendocrine system. Brain tissue was collected from ewes at 25, 30, and 35 wk of age (n=6/group). Patterns of LH release in circulation were determined on the day before euthanasia and cells containing Kiss1-mRNA were identified by in situ hybridization. Mean concentrations of LH and the frequency of LH pulses increased (P 6 pulses/12 h) of LH pulses. In Experiment 2, 28-wk-old ewe lambs were used to determine the effects of intermittent injections of kisspeptin on the release of LH and stimulation of gonadal function in peripubertal ewe lambs. Ewe lambs were treated intravenously with saline (Controls; n=6) or kisspeptin (n=6) hourly for 24 h. Blood samples were collected throughout the experiment for hormone analysis. Kisspeptin-treated lambs had greater (P < 0.02) mean circulating concentrations of LH, and frequency and amplitude of LH pulses than controls. Four of six kisspeptin-treated ewe lambs exhibited LH surge and luteal activity in response to treatments. However, onset of regular estrous cycles was not established immediately following kisspeptin-induced ovulation and no difference in age at onset of puberty was observed between groups. In conclusion, activation of the hypothalamic kisspeptin system may support elevated episodic release of LH critical for establishment of normal estrous cycle during pubertal development