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Department of Metabolic Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom
Address all correspondence and requests for reprints to: Prof. S. R. Bloom, Department of Metabolic Medicine, Faculty of Medicine, Imperial College London, 6th Floor Commonwealth Building, Hammersmith Hospital, Du Cane Road, London W12 ONN, United Kingdom. E-mail: s.bloom{at}imperial.ac.uk.
Context: Mutation of the G protein-coupled receptor 54 is associated with a failure of reproductive function. The endogenous neuropeptide agonist for G protein-coupled receptor 54, kisspeptin, potently stimulates the hypothalamic-pituitary-gonadal axis in rodents and primates.
Objective: The present study was designed to determine the effects of elevating circulating kisspeptin levels on LH, FSH, and testosterone in male volunteers.
Design: This was a double-blind, placebo-controlled, crossover study.
Setting: This was a hospital-based study.
Participants: Male volunteers (n = 6) were recruited.
Interventions: Each volunteer received a 90-min iv infusion of kisspeptin-54 (4 pmol/kg·min) and a control infusion of saline (0.9%) in random order.
Main Outcome Measure: Plasma LH, FSH, and testosterone concentrations were measured.
Results: Kisspeptin-54 infusion significantly increased plasma LH, FSH, and testosterone concentrations compared with saline infusion (mean 90-min LH: kisspeptin, 10.8 ± 1.5 vs. saline, 4.2 ± 0.5 U/liter, P < 0.001; mean 90-min FSH: kisspeptin, 3.9 ± 0.7 vs. saline, 3.2 ± 0.6 U/liter, P < 0.001; mean 180-min testosterone: kisspeptin, 24.9 ± 1.7 vs. saline, 21.7 ± 2.2 nmol/liter, P < 0.001). The plasma half-life of kisspeptin-54 was calculated to be 27.6 ± 1.1 min. The mean metabolic clearance rate was 3.2 ± 0.2 ml/kg·min, and the volume of distribution was 128.9 ± 12.5 ml/kg.
Conclusion: Elevation of plasma concentrations of kisspeptin in human males significantly increases circulating LH, FSH, and testosterone levels. Kisspeptin infusion provides a novel mechanism for hypothalamic-pituitary-gonadal axis manipulation in disorders of the reproductive system.
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