PMID- 23959940
OWN - NLM
STAT- MEDLINE
DCOM- 20140108
LR  - 20211021
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 154
IP  - 11
DP  - 2013 Nov
TI  - Kisspeptin, neurokinin B, and dynorphin act in the arcuate nucleus to control 
      activity of the GnRH pulse generator in ewes.
PG  - 4259-69
LID - 10.1210/en.2013-1331 [doi]
AB  - Recent work has led to the hypothesis that kisspeptin/neurokinin B/dynorphin 
      (KNDy) neurons in the arcuate nucleus play a key role in GnRH pulse generation, 
      with kisspeptin driving GnRH release and neurokinin B (NKB) and dynorphin acting 
      as start and stop signals, respectively. In this study, we tested this hypothesis 
      by determining the actions, if any, of four neurotransmitters found in KNDy 
      neurons (kisspeptin, NKB, dynorphin, and glutamate) on episodic LH secretion 
      using local administration of agonists and antagonists to receptors for these 
      transmitters in ovariectomized ewes. We also obtained evidence that 
      GnRH-containing afferents contact KNDy neurons, so we tested the role of two 
      components of these afferents: GnRH and orphanin-FQ. Microimplants of a Kiss1r 
      antagonist briefly inhibited LH pulses and microinjections of 2 nmol of this 
      antagonist produced a modest transitory decrease in LH pulse frequency. An 
      antagonist to the NKB receptor also decreased LH pulse frequency, whereas NKB and 
      an antagonist to the receptor for dynorphin both increased pulse frequency. In 
      contrast, antagonists to GnRH receptors, orphanin-FQ receptors, and the 
      N-methyl-D-aspartate glutamate receptor had no effect on episodic LH secretion. 
      We thus conclude that the KNDy neuropeptides act in the arcuate nucleus to 
      control episodic GnRH secretion in the ewe, but afferent input from GnRH neurons 
      to this area does not. These data support the proposed roles for NKB and 
      dynorphin within the KNDy neural network and raise the possibility that 
      kisspeptin contributes to the control of GnRH pulse frequency in addition to its 
      established role as an output signal from KNDy neurons that drives GnRH pulses.
FAU - Goodman, Robert L
AU  - Goodman RL
AD  - PhD, Department of Physiology and Pharmacology, PO Box 9229, West Virginia 
      University, Morgantown, West Virginia 26506. rgoodman@hsc.wvu.edu.
FAU - Hileman, Stanley M
AU  - Hileman SM
FAU - Nestor, Casey C
AU  - Nestor CC
FAU - Porter, Katrina L
AU  - Porter KL
FAU - Connors, John M
AU  - Connors JM
FAU - Hardy, Steve L
AU  - Hardy SL
FAU - Millar, Robert P
AU  - Millar RP
FAU - Cernea, Maria
AU  - Cernea M
FAU - Coolen, Lique M
AU  - Coolen LM
FAU - Lehman, Michael N
AU  - Lehman MN
LA  - eng
GR  - R01 HD017864/HD/NICHD NIH HHS/United States
GR  - R01 HD039916/HD/NICHD NIH HHS/United States
GR  - R01-HD017864/HD/NICHD NIH HHS/United States
GR  - R01-HD039916/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130819
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Kisspeptins)
RN  - 0 (Receptors, Neurokinin-3)
RN  - 0 (Receptors, Opioid, kappa)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 74913-18-1 (Dynorphins)
RN  - 86933-75-7 (Neurokinin B)
SB  - IM
MH  - Animals
MH  - Arcuate Nucleus of Hypothalamus/cytology/*physiology
MH  - Dynorphins/genetics/*metabolism
MH  - Female
MH  - Gonadotropin-Releasing Hormone/genetics/*metabolism
MH  - Kisspeptins/genetics/*metabolism
MH  - N-Methylaspartate/genetics/metabolism
MH  - Neurokinin B/genetics/*metabolism
MH  - Neurons/classification/metabolism
MH  - Receptors, Neurokinin-3/genetics/metabolism
MH  - Receptors, Opioid, kappa/genetics/metabolism
MH  - Sheep/*physiology
PMC - PMC3800763
EDAT- 2013/08/21 06:00
MHDA- 2014/01/09 06:00
PMCR- 2014/11/01
CRDT- 2013/08/21 06:00
PHST- 2013/08/21 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/01/09 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - en.2013-1331 [pii]
AID - EN-13-1331 [pii]
AID - 10.1210/en.2013-1331 [doi]
PST - ppublish
SO  - Endocrinology. 2013 Nov;154(11):4259-69. doi: 10.1210/en.2013-1331. Epub 2013 Aug 
      19.