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J Clin Endocrinol Metab. 2005 Dec;90(12):6609-15. Epub 2005 Sep 20.

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

Author information

1
Department of Metabolic Medicine, Faculty of Medicine, Imperial College London, London W12 ONN, United Kingdom.

Abstract

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.

PMID:
16174713
DOI:
10.1210/jc.2005-1468
[Indexed for MEDLINE]

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