Kisspeptin Stimulates the Pulsatile Secretion of Luteinizing Hormone (LH) during Postpartum Anestrus in Ewes Undergoing Continuous and Restricted Suckling

Simple Summary One of the major impediments to improving the efficiency of sheep production systems is the difficulty of breeding the females before their young are weaned. A major physiological barrier is suckling, because it prevents the initiation of a new reproductive cycle by inhibiting the pulsatile secretion of gonadotropin-releasing hormone (GnRH) and thus the secretion of LH pulses. It has now become clear that, at brain level, the secretion of GnRH is controlled primarily by the neuropeptide kisspeptin (Kp), a central player in the 'KNDy' system that generates GnRH pulses. Here, we report that intravenous administration of Kp stimulates pulsatile LH secretion in ewes during postpartum anestrus. Moreover, the response was greater when suckling was restricted to 30 min twice a day. We conclude that kisspeptin application increases pulsatile LH secretion in suckling ewes, suggesting that suckling inhibits ovulation by reducing the activity of kisspeptin neurons. This study tested whether the intravenous application of kisspeptin can stimulate the pulsatile secretion of LH in suckling ewes during postpartum anestrus. Ten days after lambing, Pelibuey ewes were allocated among two groups: (1) continuous suckling (n = 8), where the lambs remained with their mothers; and (2) restricted suckling (n = 8), where the mothers suckled their lambs twice daily for 30 min. On Day 19 postpartum, the ewes were individually penned with ad libitum access to water and feed and given an indwelling catheter in each jugular vein. On Day 20, 4 mL of blood was sampled every 15 min from 08:00 to 20:00 h to determine LH pulse frequency. At 14:00 h, four ewes in each group received 120 mu g of kisspeptin diluted in 3 mL of saline as a continuous infusion for 6 h; the remaining four ewes in each group received only saline. The interaction between kisspeptin and suckling type did not affect LH pulse frequency (p > 0.05). Before kisspeptin administration, pulse frequency was similar in all groups (1.50 +/- 0.40 pulses per 6 h; p > 0.05). With the application of kisspeptin, pulse frequency increased to 3.50 +/- 0.43 pulses per 6 h (p <= 0.014), so the concentration of LH (1.11 +/- 0.14 ng mL(-1)) was greater in kisspeptin-treated ewes than in saline-treated ewes (0.724 +/- 0.07 ng mL(-1); p <= 0.040). The frequency of LH pulses was greater with restricted suckling than with continuous suckling (2.44 +/- 0.29 versus 1.69 +/- 0.29 pulses per 6 h; p <= 0.040). We conclude that intravenous application of kisspeptin increases the pulsatile secretion of LH in suckling ewes and that suckling might reduce kisspeptin neuronal activity, perhaps explaining the suppression of ovulation. Moreover, the effects of kisspeptin and suckling on pulsatile LH secretion appear to be independent, perhaps operating through different neural pathways.