Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2006) 11 P681

Imperial College London, London, United Kingdom.

Mutation of the GPR54 receptor is associated with a failure of reproductive function. The endogenous neuropeptide agonist for GPR54, kisspeptin, potently stimulates the hypothalamic-pituitary-gonadal (HPG) 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.

Method: Study (i) Volunteers were infused with a 90 minute infusion of kisspeptin-54 (0.125, 0.25, 0.5, 1, 2, 4, 8, 12, 18, 27 or 40 pmol/kg/min, n=3 per dose). Blood was sampled for LH. Study (ii) Volunteers (n=6) received a 90 minute intravenous infusion of kisspeptin-54 (4 pmol/kg/min) and a control infusion of saline (0.9%) at least 3 days apart in random order. Blood was sampled for kisspeptin, LH, FSH and testosterone measurements. This study was approved by the local Ethical Committee.

Results: (i) There was a dose-dependent increase in mean LH over time from an infusion rate of 0.25−1.min−1 up to 4 pmol/kg/min. The latter dose of kisspeptin-54 was chosen for study (ii) as it was the lowest infusion dose which maximally increased LH levels in male volunteers.

(ii) Kisspeptin-54 infusion significantly increased plasma LH, FSH and testosterone concentrations compared to saline infusion (mean 90 minute LH: kisspeptin 10.8±1.5 vs saline 4.2±0.5 U/l, P<0.001; mean 90 minute FSH: kisspeptin 3.9±0.7 vs saline 3.2±0.6 U/l, P<0.001; mean 180 minute testosterone: kisspeptin 24.9±1.7 vs saline 21.7±2.2 nmol/l, P<0.001). The plasma half-life of kisspeptin-54 was calculated to be 27.6±1.1 min. The mean metabolic clearance rate (MCR) was 3.2±0.2 ml/kg/min and the volume of distribution (VD) 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 HPG axis manipulation in disorders of the reproductive system.

Volume 11

8th European Congress of Endocrinology incorporating the British Endocrine Societies

European Society of Endocrinology 
British Endocrine Societies 

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