Imperial College London
Alternate

ProfessorWaljitDhillo

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Endocrinology & Metabolism
 
 
 
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Contact

 

+44 (0)20 7594 3487w.dhillo Website

 
 
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Assistant

 

Ms Suzanne Wheeler +44 (0)20 7594 3487

 
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Location

 

6N6ECommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Narayanaswamy:2016:10.1210/jc.2016-1911#sthash.jYpF4p2d.dpuf,
author = {Narayanaswamy, S and Prague, J and Jayasena, C and Papadopoulou, D and Mizamtsidi, M and Shah, A and Bassett, P and COMNINOS, A and Abbara, A and Bloom, S and Veldhuis, J and Dhillo, WS},
doi = {10.1210/jc.2016-1911#sthash.jYpF4p2d.dpuf},
journal = {Journal of Clinical Endocrinology & Metabolism},
pages = {3429--3436},
title = {Investigating the KNDy hypothesis in humans by co-administration of kisspeptin, neurokinin B and naltrexone in men},
url = {http://dx.doi.org/10.1210/jc.2016-1911#sthash.jYpF4p2d.dpuf},
volume = {101},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Context: A subpopulation of hypothalamic neurons co-localise three neuropeptides namely kisspeptin, neurokinin B (NKB) and dynorphin collectively termed KNDy neurons. Animal studies suggest they interact to affect pulsatile GnRH release (KNDy hypothesis); kisspeptin stimulates, NKB modulates and dynorphin (an opioid) inhibits. Objective: To investigate the KNDy hypothesis in humans, we assessed for the first time the effects of co-administration of kisspeptin-54, NKB and an opioid receptor antagonist, naltrexone on LH pulsatility (surrogate marker for GnRH pulsatility) and gonadotropin release. Design, setting and participants: Ethically approved prospective, single-blinded placebo-controlled study. Healthy male volunteers (n=5/group) attended our research facility for 8 study visits. Intervention and main outcome measure: After 1h baseline blood sampling, participants received a different intervention at each visit: oral 50mg naltrexone (NAL), 8h intravenous infusions of vehicle, 2.56nmol/kg/h NKB (NKB), 0.1nmol/kg/h kissspeptin-54 (KP) alone and in combination. Frequent blood sampling to measure plasma gonadotropins and sex steroids was conducted and LH pulsatility was determined using blinded deconvolution analysis. Results: All kisspeptin and naltrexone containing groups potently increased LH and LH pulsatility (p<0.001 vs vehicle). NKB alone did not affect gonadotropins. NKB+KP had significantly lower increases in gonadotropins compared with kisspeptin alone (p<0.01).  NAL+KP was the only group to significantly increase LH pulse amplitude (p<0.001 vs vehicle).Conclusions: Our results suggest significant interactions between the KNDy neuropeptides on LH pulsatility and gonadotropin release in humans. This has important implications for improving our understanding of GnRH pulse generation in humans.
AU  - Narayanaswamy,S
AU  - Prague,J
AU  - Jayasena,C
AU  - Papadopoulou,D
AU  - Mizamtsidi,M
AU  - Shah,A
AU  - Bassett,P
AU  - COMNINOS,A
AU  - Abbara,A
AU  - Bloom,S
AU  - Veldhuis,J
AU  - Dhillo,WS
DO  - 10.1210/jc.2016-1911#sthash.jYpF4p2d.dpuf
EP  - 3436
PY  - 2016///
SN  - 1945-7197
SP  - 3429
TI  - Investigating the KNDy hypothesis in humans by co-administration of kisspeptin, neurokinin B and naltrexone in men
T2  - Journal of Clinical Endocrinology & Metabolism
UR  - http://dx.doi.org/10.1210/jc.2016-1911#sthash.jYpF4p2d.dpuf
UR  - http://hdl.handle.net/10044/1/34568
VL  - 101
ER  -
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