Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat

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dc.contributor.authorLi, Xiao-Fengen_ZA
dc.contributor.authorKinsey-Jones, James Sen_ZA
dc.contributor.authorCheng, Yewsongen_ZA
dc.contributor.authorKnox, Alice M Ien_ZA
dc.contributor.authorLin, Yuanshaoen_ZA
dc.contributor.authorPetrou, Nikoletta Aen_ZA
dc.contributor.authorRoseweir, Antoniaen_ZA
dc.contributor.authorLightman, Stafford Len_ZA
dc.contributor.authorMilligan, Stuart Ren_ZA
dc.contributor.authorMillar, Robert Pen_ZA
dc.date.accessioned2016-01-02T05:07:45Z
dc.date.available2016-01-02T05:07:45Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND: Kisspeptin and its G protein-coupled receptor (GPR) 54 are essential for activation of the hypothalamo-pituitary-gonadal axis. In the rat, the kisspeptin neurons critical for gonadotropin secretion are located in the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei. As the ARC is known to be the site of the gonadotropin-releasing hormone (GnRH) pulse generator we explored whether kisspeptin-GPR54 signalling in the ARC regulates GnRH pulses. METHODOLOGY/PRINCIPAL FINDINGS: We examined the effects of kisspeptin-10 or a selective kisspeptin antagonist administration intra-ARC or intra-medial preoptic area (mPOA), (which includes the AVPV), on pulsatile luteinizing hormone (LH) secretion in the rat. Ovariectomized rats with subcutaneous 17β-estradiol capsules were chronically implanted with bilateral intra-ARC or intra-mPOA cannulae, or intra-cerebroventricular (icv) cannulae and intravenous catheters. Blood samples were collected every 5 min for 5-8 h for LH measurement. After 2 h of control blood sampling, kisspeptin-10 or kisspeptin antagonist was administered via pre-implanted cannulae. Intranuclear administration of kisspeptin-10 resulted in a dose-dependent increase in circulating levels of LH lasting approximately 1 h, before recovering to a normal pulsatile pattern of circulating LH. Both icv and intra-ARC administration of kisspeptin antagonist suppressed LH pulse frequency profoundly. However, intra-mPOA administration of kisspeptin antagonist did not affect pulsatile LH secretion. Conclusions/Significance These data are the first to identify the arcuate nucleus as a key site for kisspeptin modulation of LH pulse frequency, supporting the notion that kisspeptin-GPR54 signalling in this region of the mediobasal hypothalamus is a critical neural component of the hypothalamic GnRH pulse generator.en_ZA
dc.identifier.apacitationLi, X., Kinsey-Jones, J. S., Cheng, Y., Knox, A. M. I., Lin, Y., Petrou, N. A., ... Millar, R. P. (2009). Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat. <i>PLoS One</i>, http://hdl.handle.net/11427/16181en_ZA
dc.identifier.chicagocitationLi, Xiao-Feng, James S Kinsey-Jones, Yewsong Cheng, Alice M I Knox, Yuanshao Lin, Nikoletta A Petrou, Antonia Roseweir, Stafford L Lightman, Stuart R Milligan, and Robert P Millar "Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat." <i>PLoS One</i> (2009) http://hdl.handle.net/11427/16181en_ZA
dc.identifier.citationLi, X. F., Kinsey-Jones, J. S., Cheng, Y., Knox, A. M., Lin, Y., Petrou, N. A., ... & O’Byrne, K. T. (2009). Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat. PloS one, 4(12), e8334. doi:10.1371/journal.pone.0008334en_ZA
dc.identifier.ris TY - Journal Article AU - Li, Xiao-Feng AU - Kinsey-Jones, James S AU - Cheng, Yewsong AU - Knox, Alice M I AU - Lin, Yuanshao AU - Petrou, Nikoletta A AU - Roseweir, Antonia AU - Lightman, Stafford L AU - Milligan, Stuart R AU - Millar, Robert P AB - BACKGROUND: Kisspeptin and its G protein-coupled receptor (GPR) 54 are essential for activation of the hypothalamo-pituitary-gonadal axis. In the rat, the kisspeptin neurons critical for gonadotropin secretion are located in the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei. As the ARC is known to be the site of the gonadotropin-releasing hormone (GnRH) pulse generator we explored whether kisspeptin-GPR54 signalling in the ARC regulates GnRH pulses. METHODOLOGY/PRINCIPAL FINDINGS: We examined the effects of kisspeptin-10 or a selective kisspeptin antagonist administration intra-ARC or intra-medial preoptic area (mPOA), (which includes the AVPV), on pulsatile luteinizing hormone (LH) secretion in the rat. Ovariectomized rats with subcutaneous 17β-estradiol capsules were chronically implanted with bilateral intra-ARC or intra-mPOA cannulae, or intra-cerebroventricular (icv) cannulae and intravenous catheters. Blood samples were collected every 5 min for 5-8 h for LH measurement. After 2 h of control blood sampling, kisspeptin-10 or kisspeptin antagonist was administered via pre-implanted cannulae. Intranuclear administration of kisspeptin-10 resulted in a dose-dependent increase in circulating levels of LH lasting approximately 1 h, before recovering to a normal pulsatile pattern of circulating LH. Both icv and intra-ARC administration of kisspeptin antagonist suppressed LH pulse frequency profoundly. However, intra-mPOA administration of kisspeptin antagonist did not affect pulsatile LH secretion. Conclusions/Significance These data are the first to identify the arcuate nucleus as a key site for kisspeptin modulation of LH pulse frequency, supporting the notion that kisspeptin-GPR54 signalling in this region of the mediobasal hypothalamus is a critical neural component of the hypothalamic GnRH pulse generator. DA - 2009 DB - OpenUCT DO - 10.1371/journal.pone.0008334 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat TI - Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat UR - http://hdl.handle.net/11427/16181 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16181
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0008334
dc.identifier.vancouvercitationLi X, Kinsey-Jones JS, Cheng Y, Knox AMI, Lin Y, Petrou NA, et al. Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat. PLoS One. 2009; http://hdl.handle.net/11427/16181.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_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© 2009 Li 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.otherSecretionen_ZA
dc.subject.otherNeuronsen_ZA
dc.subject.otherBlooden_ZA
dc.subject.otherArcuate nucleusen_ZA
dc.subject.otherOvariectomyen_ZA
dc.subject.otherPreoptic areaen_ZA
dc.subject.otherPlasticsen_ZA
dc.subject.otherCathetersen_ZA
dc.titleKisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the raten_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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