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Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.

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 i.v. infusion of kisspeptin-54 (4 pmol/kg x 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 x 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.