SFEBES2007 Oral Communications Novartis Clinical Endocrinology Award (2 abstracts)
Kisspeptin-54 potently stimulates luteinising hormone release during the preovulatory phase of the menstrual cycle in healthy human females.
Owais Chaudhri 1 , Waljit Dhillo 1 , Emily Thompson 1 , Kevin Murphy 1 , Victoria Salem 1 , Michael Patterson 1 , Mandy Donaldson 2 , Vian Amber 1 , Radha Ramachandran 1 , Gurjinder Nijher 1 , Alexander Kokkinos 3 , Mohammad Ghatei 1 & Steve Bloom 1
1Dept of Metabolic Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom; 2Dept of Chemical Pathology, Hammersmith Hospitals NHS Trust, London, United Kingdom; 3University of Athens, Athens, Greece.
Kisspeptin, the endogenous ligand of the GPR54 receptor, is a key regulator of the hypothalamo-pituitary-gonadal (HPG) axis. GPR54-null mice exhibit reproductive dysfunction and exogenous kisspeptin potently stimulates the HPG axis in rodents, primates and human males. The effects of kisspeptin administration to human females are not known.
Aim: To investigate the effects of kisspeptin on luteinising hormone (LH) release during the menstrual cycle in female volunteers.
Methods: (1) Volunteers received a sc bolus injection of kisspeptin-54 (0, 0.2, 0.4, 0.8, 1.6, 3.2, 6.4, 12.8 nmol/kg, n=3 per dose) in the follicular phase.
(2) Volunteers (n=6) attended on six occasions each: twice in each of the follicular, preovulatory and luteal phases. They received a sc bolus injection of either kisspeptin-54 (0.4 nmol/kg) or 0.9% saline in random order during each phase of the menstrual cycle. The local ethics committee approved this study.
Results: (1) Kisspeptin-54 caused a dose-dependent increase in mean LH over time at doses from 0.2 to 6.4 nmol/kg.
(2) Kisspeptin-54 increased plasma LH compared to saline injection in all phases of the cycle. Sensitivity to kisspeptin was greatest in the preovulatory phase and least in the follicular phase of the cycle [mean increase in LH over baseline (IU/L) ± S.E.M.: follicular phase: 0.12±0.17; preovulatory phase: 20.64±2.91 (P<0.001 vs follicular phase); luteal phase: 2.17±0.79 (P<0.01 vs follicular phase)].
Conclusion: This is the first report demonstrating that elevation of plasma kisspeptin in human females potently stimulates LH release in the preovulatory phase. We also demonstrated that subcutaneous injection is a feasible route of administration of kisspeptin-54. Thus kisspeptin may form the basis of a novel therapy for infertility.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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