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Kisspeptin signaling is required for the luteinizing hormone response in anestrous ewes following the introduction of males.

De Bond JA, Li Q, Millar RP, Clarke IJ, Smith JT - PLoS ONE (2013)

Bottom Line: 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.Brains were collected after the male effect stimulus and we observed an increase in the percentage of kisspeptin neurons co-expressing Fos, by immunohistochemistry.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Monash University, Melbourne, Victoria, Australia.

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.

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Male exposure in anestrous ewes increased the number of kisspeptin cells in the rostral ARC.The number of detectable kisspeptin neurons in the rostral ARC (A) was higher (P<0.05) in ewes exposed to males compared to control aCSF treated ewes. The number of kisspeptin neurons did not differ in the mid (B), or caudal (C) ARC. Data are the mean ± SEM, n = 4 per group.
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pone-0057972-g005: Male exposure in anestrous ewes increased the number of kisspeptin cells in the rostral ARC.The number of detectable kisspeptin neurons in the rostral ARC (A) was higher (P<0.05) in ewes exposed to males compared to control aCSF treated ewes. The number of kisspeptin neurons did not differ in the mid (B), or caudal (C) ARC. Data are the mean ± SEM, n = 4 per group.

Mentions: Kisspeptin protein expression. Kisspeptin-ir neurons in the ARC were examined following kisspeptin/Fos double-label immunocytochemistry. The number of kisspeptin neurons in the rostral ARC was higher (P<0.05) in ewes exposed to males compared to control aCSF treated ewes (Figure 5A). The number of kisspeptin neurons in the mid and caudal ARC did not differ with male exposure or treatment with the kisspeptin antagonist P-271 (Figure 5B, C). To confirm the change in kisspeptin protein expression, we repeated the experiment using single-label kisspeptin immunocytochemistry (Supporting Figure S1).


Kisspeptin signaling is required for the luteinizing hormone response in anestrous ewes following the introduction of males.

De Bond JA, Li Q, Millar RP, Clarke IJ, Smith JT - PLoS ONE (2013)

Male exposure in anestrous ewes increased the number of kisspeptin cells in the rostral ARC.The number of detectable kisspeptin neurons in the rostral ARC (A) was higher (P<0.05) in ewes exposed to males compared to control aCSF treated ewes. The number of kisspeptin neurons did not differ in the mid (B), or caudal (C) ARC. Data are the mean ± SEM, n = 4 per group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585258&req=5

pone-0057972-g005: Male exposure in anestrous ewes increased the number of kisspeptin cells in the rostral ARC.The number of detectable kisspeptin neurons in the rostral ARC (A) was higher (P<0.05) in ewes exposed to males compared to control aCSF treated ewes. The number of kisspeptin neurons did not differ in the mid (B), or caudal (C) ARC. Data are the mean ± SEM, n = 4 per group.
Mentions: Kisspeptin protein expression. Kisspeptin-ir neurons in the ARC were examined following kisspeptin/Fos double-label immunocytochemistry. The number of kisspeptin neurons in the rostral ARC was higher (P<0.05) in ewes exposed to males compared to control aCSF treated ewes (Figure 5A). The number of kisspeptin neurons in the mid and caudal ARC did not differ with male exposure or treatment with the kisspeptin antagonist P-271 (Figure 5B, C). To confirm the change in kisspeptin protein expression, we repeated the experiment using single-label kisspeptin immunocytochemistry (Supporting Figure S1).

Bottom Line: 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.Brains were collected after the male effect stimulus and we observed an increase in the percentage of kisspeptin neurons co-expressing Fos, by immunohistochemistry.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Monash University, Melbourne, Victoria, Australia.

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.

Show MeSH
Related in: MedlinePlus