Kisspeptin Signaling Is Required for the Luteinizing Hormone Response in Anestrous Ewes following the Introduction of Males

Abstract

The introduction of a novel male stimulates the hypothalamic-pituitary-gonadal axis of female sheep during seasonal anestrus, leading to the resumption of follicle maturation and ovulation. How this pheromone cue activates pulsatile secretion of gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH) is unknown. We hypothesised that pheromones activate kisspeptin neurons, the product of which is critical for the stimulation of GnRH neurons and fertility. During the non-breeding season, female sheep were exposed to novel males and blood samples collected for analysis of plasma LH profiles. Females without exposure to males served as controls. In addition, one hour before male exposure, a kisspeptin antagonist (P-271) or vehicle was infused into the lateral ventricle and continued for the entire period of male exposure. Introduction of a male led to elevated mean LH levels, due to increased LH pulse amplitude and pulse frequency in females, when compared to females not exposed to a male. Infusion of P-271 abolished this effect of male exposure. Brains were collected after the male effect stimulus and we observed an increase in the percentage of kisspeptin neurons co-expressing Fos, by immunohistochemistry. In addition, the per-cell expression of Kiss1 mRNA was increased in the rostral and mid (but not the caudal) arcuate nucleus (ARC) after male exposure in both aCSF and P-271 treated ewes, but the per-cell content of neurokinin B mRNA was decreased. There was also a generalized increase in Fos positive cells in the rostral and mid ARC as well as the ventromedial hypothalamus of females exposed to males. We conclude that introduction of male sheep to seasonally anestrous female sheep activates kisspeptin neurons and other cells in the hypothalamus, leading to increased GnRH/LH secretion.

Effects of Exposure to Male Goat Hair Extracts on Luteinizing Hormone Secretion and Neuronal Activation in Seasonally Anestrous Ewes

“…The present results are also partially comparable, in terms of the activation of the vomeronasal system, to previous studies in sheep [8, 13], in which the ram was introduced to the ewe’s pen. However, there are several discrepancies between the present results and those of previous studies, regardless of the fact that both the male goat hair extract and presence of the ram similarly facilitated pulsatile LH secretion in seasonally anestrous ewes.…”

Tachykinin: recent developments and novel roles in health and disease

“…Pheromone exposure, by the introduction of male sheep, caused an elevation in LH level in ewes during seasonal anestrus; however, pretreatment with a kisspeptin antagonist into the lateral ventricles in the ewes abolished this elevation in LH (144). After male exposure, Kiss1 mRNA was increased in the ARC, whereas NKB mRNA was decreased.…”

Lack of evidence for a role of olfaction on first maturation in farmed sea bass Dicentrarchus labrax

“…Furthermore, kiss2 was much more efficient than kiss1 in stimulating FSH and LH secretion in prepubertal sea bass (Felip et al, 2009). Recent research revealing that olfactory stimulation of female sheep with male odors increased kisspeptin expression in the brain (De Bond et al, 2013) and the anosmia inhibition of KISS2 expression are indicative of a link between olfaction and the kisspeptin pathway for gonadotropin release, although at least in sea bass this link may not be essential for reproductive success.…”