title: Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.
abstract: 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.
authors.affiliation: Department of Metabolic Medicine, Faculty of Medicine, Imperial College London, London W12 ONN, United Kingdom.
authors.forename: Waljit S
authors.initials: WS
authors.lastname: Dhillo
authors.forename: Owais B
authors.initials: OB
authors.lastname: Chaudhri
authors.forename: Michael
authors.initials: M
authors.lastname: Patterson
authors.forename: Emily L
authors.initials: EL
authors.lastname: Thompson
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Murphy
authors.forename: Michael K
authors.initials: MK
authors.lastname: Badman
authors.forename: Barbara M
authors.initials: BM
authors.lastname: McGowan
authors.forename: Vian
authors.initials: V
authors.lastname: Amber
authors.forename: Sejal
authors.initials: S
authors.lastname: Patel
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: 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
chemical_list: 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