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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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Central infusion of kisspeptin antagonist (P-271) blocks the male effect in anestrous ewes.A, Plasma LH profiles are shown in representative animals treated with artificial cerebrospinal fluid (aCSF) or P-271. The timing of infusion is indicated by the arrowhead/bar, the shaded area indicates male exposure. B–D, Mean LH, LH pulse frequency and pulse amplitude post male exposure. Data are the mean ± SEM, *P<0.05, **P<0.01, ***P<0.001, n = 4 per group.
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pone-0057972-g001: Central infusion of kisspeptin antagonist (P-271) blocks the male effect in anestrous ewes.A, Plasma LH profiles are shown in representative animals treated with artificial cerebrospinal fluid (aCSF) or P-271. The timing of infusion is indicated by the arrowhead/bar, the shaded area indicates male exposure. B–D, Mean LH, LH pulse frequency and pulse amplitude post male exposure. Data are the mean ± SEM, *P<0.05, **P<0.01, ***P<0.001, n = 4 per group.

Mentions: LH profiles are shown for 6 representative ewes in Figure 1A and were typical for anestrous ewes in the control aCSF group and all animals prior to male exposure. Pulsatile secretory episodes of LH were evident in animals immediately following the introduction of males (mean onset of the first pulse 17.5 ± 4.8 min post-male exposure) and infusion of P-271 abolished this effect (Figure 1A). Mean plasma LH levels (Figure 1B), LH pulse frequency (Figure 1C), and LH pulse amplitude (Figure 1D) increased in response to male exposure and were significantly higher (P<0.05) than in control aCSF animals. Pulse parameters in P-271-infused animals were similar to those in control aCSF-infused animals (Figures 1B–D).


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)

Central infusion of kisspeptin antagonist (P-271) blocks the male effect in anestrous ewes.A, Plasma LH profiles are shown in representative animals treated with artificial cerebrospinal fluid (aCSF) or P-271. The timing of infusion is indicated by the arrowhead/bar, the shaded area indicates male exposure. B–D, Mean LH, LH pulse frequency and pulse amplitude post male exposure. Data are the mean ± SEM, *P<0.05, **P<0.01, ***P<0.001, n = 4 per group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585258&req=5

pone-0057972-g001: Central infusion of kisspeptin antagonist (P-271) blocks the male effect in anestrous ewes.A, Plasma LH profiles are shown in representative animals treated with artificial cerebrospinal fluid (aCSF) or P-271. The timing of infusion is indicated by the arrowhead/bar, the shaded area indicates male exposure. B–D, Mean LH, LH pulse frequency and pulse amplitude post male exposure. Data are the mean ± SEM, *P<0.05, **P<0.01, ***P<0.001, n = 4 per group.
Mentions: LH profiles are shown for 6 representative ewes in Figure 1A and were typical for anestrous ewes in the control aCSF group and all animals prior to male exposure. Pulsatile secretory episodes of LH were evident in animals immediately following the introduction of males (mean onset of the first pulse 17.5 ± 4.8 min post-male exposure) and infusion of P-271 abolished this effect (Figure 1A). Mean plasma LH levels (Figure 1B), LH pulse frequency (Figure 1C), and LH pulse amplitude (Figure 1D) increased in response to male exposure and were significantly higher (P<0.05) than in control aCSF animals. Pulse parameters in P-271-infused animals were similar to those in control aCSF-infused animals (Figures 1B–D).

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