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

• Published in: The journal of clinical endocrinology and metabolism Vol. 90; no. 12; pp. 6609 - 6615
• Main Authors: Dhillo, Waljit S., Chaudhri, Owais B., Patterson, Michael, Thompson, Emily L., Murphy, Kevin G., Badman, Michael K., McGowan, Barbara M., Amber, Vian, Patel, Sejal, Ghatei, Mohammad A., Bloom, Stephen R.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-12-2005; Copyright by The Endocrine Society
• Subjects: Adult; Biological and medical sciences; Cross-Over Studies; Dose-Response Relationship, Drug; Endocrinopathies; Follicle Stimulating Hormone - blood; Fundamental and applied biological sciences. Psychology; Half-Life; Humans; Hypothalamo-Hypophyseal System - drug effects; Infusions, Intravenous; Kisspeptins; Luteinizing Hormone - blood; Male; Medical sciences; Osmolar Concentration; Pituitary-Adrenal System - drug effects; Primates; Proteins - administration & dosage; Proteins - chemistry; Proteins - metabolism; Proteins - pharmacology; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Receptors, Neuropeptide - agonists; Testosterone - blood; Time Factors; Tumor Suppressor Proteins; Vertebrates: endocrinology; Human; Male; Hypothalamohypophysogonadal axis; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2005-1468

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.