Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders.

The Journal of Clinical Investigation
A AbbaraWaljit S Dhillo

Abstract

BACKGROUNDKisspeptin 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.METHODSWe 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.RESULTSIn 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 IU∙h/...Continue Reading

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Feb 13, 2014·The Journal of Clinical Endocrinology and Metabolism·Channa N JayasenaWaljit S Dhillo
Jul 19, 2014·The Journal of Clinical Investigation·Channa N JayasenaWaljit S Dhillo
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Citations

Dec 3, 2020·Nature Reviews. Endocrinology·Claire Greenhill
Jun 18, 2021·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Valeria CalcaterraGianvincenzo Zuccotti
Jul 3, 2021·Trends in Molecular Medicine·Ali AbbaraWaljit S Dhillo
May 18, 2021·The Journal of Clinical Endocrinology and Metabolism·Graeme L FraserSteven Ramael

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Methods Mentioned

BETA
pregnancy test
transfection

Software Mentioned

WaveMetrics
GraphPad
GraphPad Prism
ImageJ
Igor Pro

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