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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2005-1468
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 12 6609-6615
Copyright © 2005 by The Endocrine Society

Kisspeptin-54 Stimulates the Hypothalamic-Pituitary Gonadal Axis in Human Males

Waljit S. Dhillo, Owais B. Chaudhri, Michael Patterson, Emily L. Thompson, Kevin G. Murphy, Michael K. Badman, Barbara M. McGowan, Vian Amber, Sejal Patel, Mohammad A. Ghatei and Stephen R. Bloom

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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