Continuous kisspeptin restores luteinizing hormone pulsatility following cessation by a neurokinin B antagonist in female sheep
dc.contributor.author | Clarke, Iain J. | |
dc.contributor.author | Li, Qun | |
dc.contributor.author | Henry, Belinda A. | |
dc.contributor.author | Millar, Robert P. | |
dc.date.accessioned | 2018-04-18T13:04:53Z | |
dc.date.issued | 2018-02 | |
dc.description.abstract | Pulsatile 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.department | Immunology | en_ZA |
dc.description.department | Physiology | en_ZA |
dc.description.embargo | 2019-02-01 | |
dc.description.librarian | hj2018 | en_ZA |
dc.description.sponsorship | The 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.uri | https://academic.oup.com/endo | en_ZA |
dc.identifier.citation | Clarke, 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.issn | 0013-7227 (print) | |
dc.identifier.issn | 1945-7170 (online) | |
dc.identifier.other | 10.1210/en.2017-00737 | |
dc.identifier.uri | http://hdl.handle.net/2263/64601 | |
dc.language.iso | en | en_ZA |
dc.publisher | Oxford University Press | en_ZA |
dc.rights | © 2018 The Endocrine Society | en_ZA |
dc.subject | Gonadotropin-releasing hormone (GnRH) | en_ZA |
dc.subject | Luteinizing hormone (LH) | en_ZA |
dc.subject | Kisspeptin (Kiss) | en_ZA |
dc.subject | Neurokinin B (NKB) | en_ZA |
dc.subject | Intravenous infusion | en_ZA |
dc.subject | In vivo | en_ZA |
dc.subject | GnRH/LH secretion | en_ZA |
dc.subject | Pulse generation | en_ZA |
dc.subject | Ovariectomized ewes | en_ZA |
dc.subject | Hypogonadotropic hypogonadism | en_ZA |
dc.subject | Arcuate nucleus | en_ZA |
dc.subject | Hypophyseal portal blood | en_ZA |
dc.title | Continuous kisspeptin restores luteinizing hormone pulsatility following cessation by a neurokinin B antagonist in female sheep | en_ZA |
dc.type | Postprint Article | en_ZA |