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{Abbara:2020:10.1172/JCI139681,
author = {Abbara, A and Eng, P and Phylactou, M and Clarke, S and Richardson, R and sykes, C and Phumsatitpong, C and Mills, E and Modi, M and Izzi-Engbeaya, C and Papadopoulou, D and Purugganan, K and Jayasena, C and Webber, L and salim, R and Owen, B and Bech, P and Comninos, A and McArdle, C and violitis, M and Tsaneva-Atanasova, K and Moenter, S and Hanyaloglu, A and Dhillo, W},
doi = {10.1172/JCI139681},
journal = {Journal of Clinical Investigation},
pages = {6739--6753},
title = {Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders.},
url = {http://dx.doi.org/10.1172/JCI139681},
volume = {130},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND. Kisspeptin is a key regulator of hypothalamic gonadotropin-releasing hormone (GnRH) neurons and is essential for reproductive health. A specific kisspeptin receptor (KISS1R) agonist could significantly expand the potential clinical utility of therapeutics targeting the kisspeptin pathway. Herein, we investigate the effects of a KISS1R agonist, MVT-602, in healthy women and in women with reproductive disorders.METHODS. We conducted in vivo and in vitro studies to characterize the action of MVT-602 in comparison with native kisspeptin-54 (KP54). We determined the pharmacokinetic and pharmacodynamic properties of MVT-602 (doses 0.01 and 0.03 nmol/kg) versus KP54 (9.6 nmol/kg) in the follicular phase of healthy women (n = 9), and in women with polycystic ovary syndrome (PCOS; n = 6) or hypothalamic amenorrhea (HA; n = 6). Further, we investigated their effects on KISS1R-mediated inositol monophosphate (IP1) and Ca2+ signaling in cell lines and on action potential firing of GnRH neurons in brain slices.RESULTS. In healthy women, the amplitude of luteinizing hormone (LH) rise was similar to that after KP54, but peaked later (21.4 vs. 4.7 hours; P = 0.0002), with correspondingly increased AUC of LH exposure (169.0 vs. 38.5 IUh/L; P = 0.0058). LH increases following MVT-602 were similar in PCOS and healthy women, but advanced in HA (P = 0.004). In keeping with the clinical data, MVT-602 induced more potent signaling of KISS1R-mediated IP1 accumulation and a longer duration of GnRH neuron firing than KP54 (115 vs. 55 minutes; P = 0.0012).CONCLUSION. Taken together, these clinical and mechanistic data identify MVT-602 as having considerable therapeutic potential for the treatment of female reproductive disorders.TRIAL REGISTRATION. International Standard Randomised Controlled Trial Number (ISRCTN) Registry, ISRCTN21681316.FUNDING. National Institute for Health Research and NIH.
AU  - Abbara,A
AU  - Eng,P
AU  - Phylactou,M
AU  - Clarke,S
AU  - Richardson,R
AU  - sykes,C
AU  - Phumsatitpong,C
AU  - Mills,E
AU  - Modi,M
AU  - Izzi-Engbeaya,C
AU  - Papadopoulou,D
AU  - Purugganan,K
AU  - Jayasena,C
AU  - Webber,L
AU  - salim,R
AU  - Owen,B
AU  - Bech,P
AU  - Comninos,A
AU  - McArdle,C
AU  - violitis,M
AU  - Tsaneva-Atanasova,K
AU  - Moenter,S
AU  - Hanyaloglu,A
AU  - Dhillo,W
DO  - 10.1172/JCI139681
EP  - 6753
PY  - 2020///
SN  - 0021-9738
SP  - 6739
TI  - Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders.
T2  - Journal of Clinical Investigation
UR  - http://dx.doi.org/10.1172/JCI139681
UR  - https://www.jci.org/articles/view/139681
UR  - http://hdl.handle.net/10044/1/83092
VL  - 130
ER  -
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