title: Effects of neurokinin B administration on reproductive hormone secretion in healthy men and women.
abstract: BACKGROUND
  Neurokinin B (NKB) is a member of the tachykinin family of peptides. Inactivating mutations in the tachykinin 3 or tachykinin 3 receptor gene are associated with pubertal failure and congenital hypogonadotrophic hypogonadism in humans. This suggests that NKB may have a critical role in human reproduction. The effects of NKB administration have not been investigated previously in humans.
  
  
  OBJECTIVE
  The aim of this study was to determine the effects of iv administration of NKB on gonadotrophin secretion in healthy male and female volunteers.
  
  
  METHODS
  A total of 23 healthy men and 11 healthy women participated in the study. After an initial dose-finding study (study 1), men received a 4-hour infusion of vehicle (gelofusin) followed by a 4-hour infusion of NKB (2.56 or 5.12 nmol/kg/h) (study 2), and an 8-hour infusion of vehicle or NKB during different visits (study 3). Healthy women underwent a dose-finding study consisting of a 3-hour NKB administration during the follicular phase of the menstrual cycle, and the maximum dose of NKB was also tested during the preovulatory and midluteal phases of menstrual cycle (study 4).
  
  
  RESULTS
  Mean LH, FSH, and T secretion were not significantly altered during a 90-minute infusion of NKB (0.4-5.12 nmol/kg/h), or a 4-hour infusion of NKB (5.12 nmol/kg/h). No alterations in gonadotrophin secretion or LH pulsatility were observed during an 8-hour infusion of NKB when compared with vehicle. Doses of 0.64-5.12 nmol/kg/h NKB did not significantly alter LH, FSH, or estradiol secretion in healthy women during the follicular phase of the menstrual cycle. Finally, 5.12 nmol/kg/h did not significantly alter reproductive hormone secretion during the preovulatory or midluteal phases of the menstrual cycle.
  
  
  CONCLUSIONS
  This is the first clinical study of NKB administration. None of the doses of NKB tested were associated with significant alterations in reproductive hormone secretion in healthy male or female volunteers. These novel data add to our understanding of the physiological actions of NKB in human reproduction.
authors.affiliation: Section of Investigative Medicine (C.N.J., A.N.C., A.D.S., A.A., G.M.K.N., Z.G.-D., M.V., M.A.G., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Department of Histopathology (G.S.), Royal Marsden Hospital, London SW3 6JJ, United Kingdom.
authors.forename: Channa N
authors.initials: CN
authors.lastname: Jayasena
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Comninos
authors.forename: Akila
authors.initials: A
authors.lastname: De Silva
authors.forename: Ali
authors.initials: A
authors.lastname: Abbara
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: Gurjinder M K
authors.initials: GM
authors.lastname: Nijher
authors.forename: Zainab
authors.initials: Z
authors.lastname: Ganiyu-Dada
authors.forename: Meriel
authors.initials: M
authors.lastname: Vaal
authors.forename: Gordon
authors.initials: G
authors.lastname: Stamp
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.forename: Waljit S
authors.initials: WS
authors.lastname: Dhillo
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005780:Gelatin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000097:blood; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008597:Menstrual Cycle / Q000187:drug effects / Q000378:metabolism; D015287:Neurokinin B / Q000008:administration & dosage* / Q000009:adverse effects; D012098:Reproduction / Q000187:drug effects*; D016037:Single-Blind Method; D013386:Succinates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D013386:Succinates; C060085:succinylated gelatin; D015287:Neurokinin B; D005780:Gelatin