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

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dc.contributor.authorDe Bond, Julie-Ann Pen_ZA
dc.contributor.authorLi, Qunen_ZA
dc.contributor.authorMillar, Robert Pen_ZA
dc.contributor.authorClarke, Iain Jen_ZA
dc.contributor.authorSmith, Jeremy Ten_ZA
dc.date.accessioned2016-01-11T06:46:11Z
dc.date.available2016-01-11T06:46:11Z
dc.date.issued2013en_ZA
dc.description.abstractThe 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.en_ZA
dc.identifier.apacitationDe Bond, J. P., Li, Q., Millar, R. P., Clarke, I. J., & Smith, J. T. (2013). Kisspeptin signaling is required for the luteinizing hormone response in anestrous ewes following the introduction of males. <i>PLoS One</i>, http://hdl.handle.net/11427/16218en_ZA
dc.identifier.chicagocitationDe Bond, Julie-Ann P, Qun Li, Robert P Millar, Iain J Clarke, and Jeremy T Smith "Kisspeptin signaling is required for the luteinizing hormone response in anestrous ewes following the introduction of males." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/16218en_ZA
dc.identifier.citationDe Bond, J. A. P., Li, Q., Millar, R. P., Clarke, I. J., & Smith, J. T. (2013).Kisspeptin signaling is required for the luteinizing hormone response in anestrous ewes following the introduction of males. PLoS ONE, 8(2), 57972. doi:10.1371/journal.pone.0057972en_ZA
dc.identifier.ris TY - Journal Article AU - De Bond, Julie-Ann P AU - Li, Qun AU - Millar, Robert P AU - Clarke, Iain J AU - Smith, Jeremy T AB - 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. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0057972 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Kisspeptin signaling is required for the luteinizing hormone response in anestrous ewes following the introduction of males TI - Kisspeptin signaling is required for the luteinizing hormone response in anestrous ewes following the introduction of males UR - http://hdl.handle.net/11427/16218 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16218
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0057972
dc.identifier.vancouvercitationDe Bond JP, Li Q, Millar RP, Clarke IJ, Smith JT. Kisspeptin signaling is required for the luteinizing hormone response in anestrous ewes following the introduction of males. PLoS One. 2013; http://hdl.handle.net/11427/16218.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentMRC/UCT Receptor Biology Research Groupen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2013 De Bond et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherNeuronsen_ZA
dc.subject.otherSecretionen_ZA
dc.subject.otherPheromonesen_ZA
dc.subject.otherSheepen_ZA
dc.subject.otherHypothalamusen_ZA
dc.subject.otherImmunocytochemistryen_ZA
dc.subject.otherGnRH stimulation testen_ZA
dc.subject.otherEstrogensen_ZA
dc.titleKisspeptin signaling is required for the luteinizing hormone response in anestrous ewes following the introduction of malesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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