title: Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men.
abstract: OBJECTIVE
  How potently does the novel hypothalamic stimulator of reproduction, kisspeptin, increase gonadotrophin secretion when compared with GnRH in healthy men?
  
  
  CONCLUSIONS
  At the doses tested, intravenous administration of either of two major kisspeptin isoforms, kisspeptin-10 and -54, was associated with similar levels of gonadotrophin secretion in healthy men; however, GnRH was more potent when compared with either kisspeptin isoform.
  
  
  BACKGROUND
  Kisspeptin-10 and -54 are naturally occurring hormones in the kisspeptin peptide family which potently stimulates endogenous GnRH secretion from the hypothalamus, so have the potential to treat patients with reproductive disorders. Rodent studies suggest that kisspeptin-54 is more potent when compared with kisspepitn-10; however, their effects have not previously been directly compared in humans, or compared with direct pituitary stimulation of gonadotrophin secretion using GnRH.
  
  
  METHODS
  A single-blinded placebo controlled physiological study was performed from January to December 2013. Local ethical approval was granted, and five participants were recruited to each dosing group.
  
  
  METHODS
  Healthy men were administered vehicle, kisspeptin-10, kisspeptin-54 and GnRH intravenously for 3 h on different study days. Each hormone was administered at 0.1, 0.3 and 1.0 nmol/kg/h doses (n = 5 subjects per group). Regular blood sampling was conducted throughout the study to measure LH and FSH. Study visits were conducted at least a week apart.
  
  
  RESULTS
  Serum LH and FSH levels were ∼3-fold higher during GnRH infusion when compared with kisspeptin-10 and ∼2-fold higher when compared with kisspeptin-54 [mean area under the curve serum LH during infusion (in hours times international units per litre, h.IU/l): 10.81 ± 1.73, 1.0 nmol/kg/h kisspeptin-10; 14.43 ± 1.27, 1.0 nmol/kg/h kisspeptin-54; 34.06 ± 5.18, 1.0 nmol/kg/h GnRH, P < 0.001 versus kisspeptin-10, P < 0.01 versus kisspeptin-54].
  
  
  CONCLUSIONS
  This study had a small sample size.
  
  
  CONCLUSIONS
  Kisspeptin offers a novel means of stimulating the reproductive axis. Our data suggest that kisspeptin stimulates gonadotrophin secretion less potently when compared with GnRH; however, kisspeptin may stimulate gonadotrophins in a more physiological manner when compared with current therapies. Kisspeptin is emerging as a future therapeutic agent, so it is important to establish which kisspeptin hormones could be used to treat patients with infertility. Results of this study suggest that either isoform has similar effects on reproductive hormone secretion in healthy men when administered intravenously.
  
  
  BACKGROUND
  This work is funded by grants from the MRC and NIHR and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. C.N.J. is supported by an NIHR Clinical Lectureship. A.A. is supported by Wellcome Trust Research Training Fellowships. A.N.C. is supported by Wellcome Trust Translational Medicine Training Fellowship. W.S.D. is supported by an NIHR Career Development Fellowship.
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.
authors.forename: C N
authors.initials: CN
authors.lastname: Jayasena
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.
authors.forename: A
authors.initials: A
authors.lastname: Abbara
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.
authors.forename: S
authors.initials: S
authors.lastname: Narayanaswamy
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.
authors.forename: A N
authors.initials: AN
authors.lastname: Comninos
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.
authors.forename: R
authors.initials: R
authors.lastname: Ratnasabapathy
authors.affiliation: Statsconsultancy Ltd, 40 Longwood Lane, Amersham, Bucks HP7 9EN, UK.
authors.forename: P
authors.initials: P
authors.lastname: Bassett
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.
authors.forename: J T
authors.initials: JT
authors.lastname: Mogford
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Malik
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.
authors.forename: J
authors.initials: J
authors.lastname: Calley
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
authors.affiliation: Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6th Floor, Commonwealth Building, London W12 0NN, UK w.dhillo@imperial.ac.uk.
authors.forename: W S
authors.initials: WS
authors.lastname: Dhillo
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D005640:Follicle Stimulating Hormone / Q000097:blood*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage*; D006801:Humans; D059648:Kisspeptins / Q000008:administration & dosage*; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: FSH; GnRH; LH; kisspeptin-10; kisspeptin-54