GPR54-dependent stimulation of luteinizing hormone secretion by neurokinin B in prepubertal rats

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dc.contributor.authorGrachev, Pashaen_ZA
dc.contributor.authorLi, Xiao Fengen_ZA
dc.contributor.authorLin, Yuan Shaoen_ZA
dc.contributor.authorHu, Ming Hanen_ZA
dc.contributor.authorElsamani, Leenaen_ZA
dc.contributor.authorPaterson, Stewart Jen_ZA
dc.contributor.authorMillar, Robert Pen_ZA
dc.contributor.authorLightman, Stafford Len_ZA
dc.contributor.authorO'Byrne, Kevin Ten_ZA
dc.date.accessioned2016-01-02T05:07:41Z
dc.date.available2016-01-02T05:07:41Z
dc.date.issued2012en_ZA
dc.description.abstractKisspeptin, neurokinin B (NKB) and dynorphin A (Dyn) are coexpressed within KNDy neurons that project from the hypothalamic arcuate nucleus (ARC) to GnRH neurons and numerous other hypothalamic targets. Each of the KNDy neuropeptides has been implicated in regulating pulsatile GnRH/LH secretion. In isolation, kisspeptin is generally known to stimulate, and Dyn to inhibit LH secretion. However, the NKB analog, senktide, has variously been reported to inhibit, stimulate or have no effect on LH secretion. In prepubertal mice, rats and monkeys, senktide stimulates LH secretion. Furthermore, in the monkey this effect is dependent on kisspeptin signaling through its receptor, GPR54. The present study tested the hypotheses that the stimulatory effects of NKB on LH secretion in intact rats are mediated by kisspeptin/GPR54 signaling and are independent of a Dyn tone. To test this, ovarian-intact prepubertal rats were subjected to frequent automated blood sampling before and after intracerebroventricular injections of KNDy neuropeptide analogs. Senktide robustly induced single LH pulses, while neither the GPR54 antagonist, Kp-234, nor the Dyn agonist and antagonist (U50488 and nor-BNI, respectively) had an effect on basal LH levels. However, Kp-234 potently blocked the senktide-induced LH pulses. Modulation of the Dyn tone by U50488 or nor-BNI did not affect the senktide-induced LH pulses. These data demonstrate that the stimulatory effect of NKB on LH secretion in intact female rats is dependent upon kisspeptin/GPR54 signaling, but not on Dyn signaling.en_ZA
dc.identifier.apacitationGrachev, P., Li, X. F., Lin, Y. S., Hu, M. H., Elsamani, L., Paterson, S. J., ... O'Byrne, K. T. (2012). GPR54-dependent stimulation of luteinizing hormone secretion by neurokinin B in prepubertal rats. <i>PLoS One</i>, http://hdl.handle.net/11427/16176en_ZA
dc.identifier.chicagocitationGrachev, Pasha, Xiao Feng Li, Yuan Shao Lin, Ming Han Hu, Leena Elsamani, Stewart J Paterson, Robert P Millar, Stafford L Lightman, and Kevin T O'Byrne "GPR54-dependent stimulation of luteinizing hormone secretion by neurokinin B in prepubertal rats." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/16176en_ZA
dc.identifier.citationGrachev, P., Li, X. F., Lin, Y. S., Hu, M. H., Elsamani, L., Paterson, S. J., ... & O’Byrne, K. T. (2012). GPR54-dependent stimulation of luteinizing hormone secretion by neurokinin B in prepubertal rats. PLoS ONE 7(9): e44344. doi:10.1371/journal.pone.0044344en_ZA
dc.identifier.ris TY - Journal Article AU - Grachev, Pasha AU - Li, Xiao Feng AU - Lin, Yuan Shao AU - Hu, Ming Han AU - Elsamani, Leena AU - Paterson, Stewart J AU - Millar, Robert P AU - Lightman, Stafford L AU - O'Byrne, Kevin T AB - Kisspeptin, neurokinin B (NKB) and dynorphin A (Dyn) are coexpressed within KNDy neurons that project from the hypothalamic arcuate nucleus (ARC) to GnRH neurons and numerous other hypothalamic targets. Each of the KNDy neuropeptides has been implicated in regulating pulsatile GnRH/LH secretion. In isolation, kisspeptin is generally known to stimulate, and Dyn to inhibit LH secretion. However, the NKB analog, senktide, has variously been reported to inhibit, stimulate or have no effect on LH secretion. In prepubertal mice, rats and monkeys, senktide stimulates LH secretion. Furthermore, in the monkey this effect is dependent on kisspeptin signaling through its receptor, GPR54. The present study tested the hypotheses that the stimulatory effects of NKB on LH secretion in intact rats are mediated by kisspeptin/GPR54 signaling and are independent of a Dyn tone. To test this, ovarian-intact prepubertal rats were subjected to frequent automated blood sampling before and after intracerebroventricular injections of KNDy neuropeptide analogs. Senktide robustly induced single LH pulses, while neither the GPR54 antagonist, Kp-234, nor the Dyn agonist and antagonist (U50488 and nor-BNI, respectively) had an effect on basal LH levels. However, Kp-234 potently blocked the senktide-induced LH pulses. Modulation of the Dyn tone by U50488 or nor-BNI did not affect the senktide-induced LH pulses. These data demonstrate that the stimulatory effect of NKB on LH secretion in intact female rats is dependent upon kisspeptin/GPR54 signaling, but not on Dyn signaling. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0044344 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - GPR54-dependent stimulation of luteinizing hormone secretion by neurokinin B in prepubertal rats TI - GPR54-dependent stimulation of luteinizing hormone secretion by neurokinin B in prepubertal rats UR - http://hdl.handle.net/11427/16176 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16176
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0044344
dc.identifier.vancouvercitationGrachev P, Li XF, Lin YS, Hu MH, Elsamani L, Paterson SJ, et al. GPR54-dependent stimulation of luteinizing hormone secretion by neurokinin B in prepubertal rats. PLoS One. 2012; http://hdl.handle.net/11427/16176.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© Grachev 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.otherAnimal signaling and communicationen_ZA
dc.subject.otherSecretion systemsen_ZA
dc.subject.otherGnRH stimulation testen_ZA
dc.subject.otherBlooden_ZA
dc.subject.otherDevelopmental signalingen_ZA
dc.subject.otherSignal inhibitionen_ZA
dc.titleGPR54-dependent stimulation of luteinizing hormone secretion by neurokinin B in prepubertal ratsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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