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


METHODS
This was a double-blind, placebo-controlled, crossover study.


METHODS
This was a hospital-based study.


METHODS
Male volunteers (n = 6) were recruited.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Dhillo
Waljit S
WS
Department of Metabolic Medicine, Faculty of Medicine, Imperial College London, London W12 ONN, United Kingdom.
Chaudhri
Owais B
OB
Patterson
Michael
M
Thompson
Emily L
EL
Murphy
Kevin G
KG
Badman
Michael K
MK
McGowan
Barbara M
BM
Amber
Vian
V
Patel
Sejal
S
Ghatei
Mohammad A
MA
Bloom
Stephen R
SR
D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000097:blood; D006207:Half-Life; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007262:Infusions, Intravenous; D059648:Kisspeptins; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009994:Osmolar Concentration; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011506:Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide / Q000819:agonists; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D025521:Tumor Suppressor Proteins
C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide; D025521:Tumor Suppressor Proteins; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone