PMID- 29126131
OWN - NLM
STAT- MEDLINE
DCOM- 20180515
LR  - 20180515
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 159
IP  - 2
DP  - 2018 Feb 1
TI  - Continuous Kisspeptin Restores Luteinizing Hormone Pulsatility Following 
      Cessation by a Neurokinin B Antagonist in Female Sheep.
PG  - 639-646
LID - 10.1210/en.2017-00737 [doi]
AB  - 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.
CI  - Copyright (c) 2018 Endocrine Society.
FAU - Clarke, Iain J
AU  - Clarke IJ
AD  - Neuroscience Program, Monash Biomedicine Discovery Institute, Monash University, 
      Melbourne, Victoria, Australia.
AD  - Department of Physiology, Monash University, Melbourne, Victoria, Australia.
FAU - Li, Qun
AU  - Li Q
AD  - Neuroscience Program, Monash Biomedicine Discovery Institute, Monash University, 
      Melbourne, Victoria, Australia.
AD  - Department of Physiology, Monash University, Melbourne, Victoria, Australia.
FAU - Henry, Belinda A
AU  - Henry BA
AD  - Department of Physiology, Monash University, Melbourne, Victoria, Australia.
AD  - Metabolic Disease and Obesity Program, Monash Biomedicine Discovery Institute, 
      Monash University, Melbourne, Victoria, Australia.
FAU - Millar, Robert P
AU  - Millar RP
AD  - Division of Medical Biochemistry, Institute for Infectious Diseases and Molecular 
      Medicine, University of Cape Town, Cape Town, South Africa.
AD  - Department of Physiology, Centre for Neuroendocrinology, University of Pretoria, 
      Pretoria, South Africa.
AD  - Department of Immunology, Centre for Neuroendocrinology, University of Pretoria, 
      Pretoria, South Africa.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Kisspeptins)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 86933-75-7 (Neurokinin B)
RN  - 9002-67-9 (Luteinizing Hormone)
SB  - IM
MH  - Animals
MH  - Female
MH  - Gonadotropin-Releasing Hormone/metabolism
MH  - Kisspeptins/*metabolism
MH  - Luteinizing Hormone/*metabolism
MH  - Neurokinin B/*metabolism
MH  - Neurons/metabolism
MH  - Sheep/*metabolism
EDAT- 2017/11/11 06:00
MHDA- 2018/05/16 06:00
CRDT- 2017/11/11 06:00
PHST- 2017/08/11 00:00 [received]
PHST- 2017/10/27 00:00 [accepted]
PHST- 2017/11/11 06:00 [pubmed]
PHST- 2018/05/16 06:00 [medline]
PHST- 2017/11/11 06:00 [entrez]
AID - 4590185 [pii]
AID - 10.1210/en.2017-00737 [doi]
PST - ppublish
SO  - Endocrinology. 2018 Feb 1;159(2):639-646. doi: 10.1210/en.2017-00737.