Continuous kisspeptin restores luteinizing hormone pulsatility following cessation by a neurokinin B antagonist in female sheep

dc.contributor.authorClarke, Iain J.
dc.contributor.authorLi, Qun
dc.contributor.authorHenry, Belinda A.
dc.contributor.authorMillar, Robert P.
dc.date.accessioned2018-04-18T13:04:53Z
dc.date.issued2018-02
dc.description.abstractPulsatile secretion of the gonadotropin-releasing hormone (GnRH) drives pulsatile secretion of the luteinizing hormone (LH), with evidence that this depends on kisspeptin (Kiss) input to GnRH neurons. Kiss administration causes acute GnRH/LH secretion, and electrophysiological data suggest that Kiss neurons may act in a phasic manner to drive GnRH secretion, but there is not definitive evidence for this. The product of the Kiss-1 gene is proteolytically cleaved to smaller products, and the 10 amino acid C-terminal product (Kiss-10) displays full bioactivity. We have shown previously that continuous delivery of Kiss-10 to anestrous ewes can cause a surge in GnRH secretion and ovulation and increases LH pulse frequency in humans. Here, we tested the hypothesis that continuous Kiss-10 delivery can support pulsatile GnRH/LH secretion in the sheep. Neurokinin B (NKB) provides positive drive to Kiss neurons, so we therefore infused an NKB antagonist (ANT-08) intracerebroventricularly to induce cessation of pulsatile GnRH/LH secretion, with or without concomitant continuous Kiss-10 infusion. ANT-08 suppressed GnRH/LH pulsatility, which was immediately restored with continuous Kiss-10 infusion. These data support the notion that Kiss-10 action is downstream of NKB signaling and that continuous Kiss-10 stimulation of GnRH neurons is sufficient to support a pulsatile pattern of GnRH/LH secretion. This offers further support to the theory that GnRH pulse generation is intrinsic to GnRH neurons and that pulsatile GnRH release can be affected with continuous stimulation by Kiss-10.en_ZA
dc.description.departmentImmunologyen_ZA
dc.description.departmentPhysiologyen_ZA
dc.description.embargo2019-02-01
dc.description.librarianhj2018en_ZA
dc.description.sponsorshipThe Universities of Pretoria and Cape Town, South African Medical Research Council, and National Research Foundation. I.J.C. was funded by the National Health and Medical Research Council of Australia.en_ZA
dc.description.urihttps://academic.oup.com/endoen_ZA
dc.identifier.citationClarke, I.J., Li, Q., Henry, B.A. & Millar, R.P. 2018, 'Continuous kisspeptin restores luteinizing hormone pulsatility following cessation by a neurokinin B antagonist in female sheep', Endocrinology, vol. 159, no. 2, pp. 639-646.en_ZA
dc.identifier.issn0013-7227 (print)
dc.identifier.issn1945-7170 (online)
dc.identifier.other10.1210/en.2017-00737
dc.identifier.urihttp://hdl.handle.net/2263/64601
dc.language.isoenen_ZA
dc.publisherOxford University Pressen_ZA
dc.rights© 2018 The Endocrine Societyen_ZA
dc.subjectGonadotropin-releasing hormone (GnRH)en_ZA
dc.subjectLuteinizing hormone (LH)en_ZA
dc.subjectKisspeptin (Kiss)en_ZA
dc.subjectNeurokinin B (NKB)en_ZA
dc.subjectIntravenous infusionen_ZA
dc.subjectIn vivoen_ZA
dc.subjectGnRH/LH secretionen_ZA
dc.subjectPulse generationen_ZA
dc.subjectOvariectomized ewesen_ZA
dc.subjectHypogonadotropic hypogonadismen_ZA
dc.subjectArcuate nucleusen_ZA
dc.subjectHypophyseal portal blooden_ZA
dc.titleContinuous kisspeptin restores luteinizing hormone pulsatility following cessation by a neurokinin B antagonist in female sheepen_ZA
dc.typePostprint Articleen_ZA

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