title: Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels.
abstract: OBJECTIVE
  Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin-54 in healthy women. Women are markedly more responsive to exogenous kisspeptin in the late follicular phase preovulation when oestradiol levels are naturally high. Therefore, we further investigated whether there was a correlation between baseline oestradiol levels and LH response to kisspeptin.
  
  
  METHODS
  A prospective, single-blinded placebo-controlled study. Healthy women (n = 4) received an 8-h SC infusion of kisspeptin-54 0·1, 0·3 or 1·0 nmol/kg/h or saline in the early follicular phase of 4 separate menstrual cycles. Gonadotrophins and oestradiol were measured every 10 min during the infusions.
  
  
  RESULTS
  SC infusion of kisspeptin-54 increased LH and FSH. The LH response to SC infusion of kisspeptin-54 (0·3 and 1·0 nmol/kg/h) positively correlated with baseline oestradiol levels (P < 0·001). Further statistical analyses showed that in the 1·0 nmol/kg/h group, a 100pmol/l rise in baseline oestradiol was associated with a 1·0 IU/l increase in LH.
  
  
  CONCLUSIONS
  Kisspeptin administered via a SC infusion could be a viable future therapeutic route of administration for patients with infertility. Baseline oestradiol levels may be an important determinant of the gonadotrophin response to kisspeptin treatment in women and should be taken into consideration when evaluating gonadotrophin response.
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Shakunthala
authors.initials: S
authors.lastname: Narayanaswamy
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Channa N
authors.initials: CN
authors.lastname: Jayasena
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Noel
authors.initials: N
authors.lastname: Ng
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Risheka
authors.initials: R
authors.lastname: Ratnasabapathy
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Prague
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Papadopoulou
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Abbara
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Comninos
authors.affiliation: Statsconsultancy Ltd, Bucks, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Bassett
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.affiliation: Endocrine Research Unit, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.affiliation: Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Waljit S
authors.initials: WS
authors.lastname: Dhillo
mesh_terms: D000293:Adolescent; D000328:Adult; D004958:Estradiol / Q000097:blood*; D005260:Female; D005498:Follicular Phase; D007987:Gonadotropin-Releasing Hormone; D006062:Gonadotropins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D055104:Infusions, Subcutaneous; D059648:Kisspeptins / Q000008:administration & dosage* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D006062:Gonadotropins; C106628:KISS1 protein, human; D059648:Kisspeptins; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone