title: Effect of gonadotropin-inhibitory hormone on luteinizing hormone secretion in humans.
abstract: BACKGROUND
  Gonadotropin-inhibitory hormone (GnIH, human homologue of RFRP-3) suppresses gonadotropin secretion in animal models, but its effects have not been studied in the human.
  
  
  OBJECTIVE
  We tested the hypotheses that exogenous GnIH inhibits LH secretion (i) in postmenopausal women and (ii) in men concurrently administered exogenous kisspeptin.
  
  
  METHODS
  Following in vitro and in vivo preclinical studies to functionally characterize the GnIH peptide, a dose-finding study (human GnIH: 1·5-150 μg/kg/h, iv for 3 h) was undertaken, and 50 μg/kg/h selected for further evaluation. Five postmenopausal women were administered 50 μg/kg/h iv infusion for 3 h or vehicle on two separate days. Four men were administered kisspeptin-10 (0·3 μg/kg iv bolus) with simultaneous infusion of GnIH (50 μg/kg/h, iv for 3 h) or vehicle.
  
  
  METHODS
  Healthy postmenopausal women (mean age 58 ± 2 years, LH: 30·8 ± 2·9 IU/l, FSH: 78·7 ± 6·4 IU/l, oestradiol: <50 pmol/l) and men (39·8 ± 2·1 years, mean total testosterone 12·1 ± 1·8 nmol/l, LH 2·2 ± 0·2 IU/l).
  
  
  METHODS
  Change in area under curve (AUC) of LH during GnIHvs vehicle.
  
  
  RESULTS
  During GnIH administration in postmenopausal women, LH secretion decreased (ΔAUC: -9·9 ± 1·8 IU/3 h) vs vehicle (ΔAUC: -0·5 ± 1·7 IU/3 h; P = 0·02). Kisspeptin-10-stimulated LH responses in men were not affected by GnIH co-administration (60-min AUC of LH 6·2 ± 0·8 IU/h with kisspeptin-10 alone, 6·3 ± 1·0 IU/h, kisspeptin-10 with GnIH, P = 0·72). Exogenous GnIH was well tolerated, with no adverse events reported.
  
  
  CONCLUSIONS
  Gonadotropin-inhibitory hormone decreased LH secretion in postmenopausal women in this first-in-human study. Kisspeptin-stimulated LH secretion in men was not inhibited during concomitant administration of GnIH.
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.|Diabetes Trials Unit, Endocrinology and Metabolism, Oxford Centre for Diabetes, Oxford, UK.
authors.forename: J T
authors.identifier: http://orcid.org/0000-0003-2570-7232
authors.initials: JT
authors.lastname: George
authors.affiliation: Department of Medical Biochemistry and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.
authors.forename: M
authors.initials: M
authors.lastname: Hendrikse
authors.affiliation: Endocrine Research Unit, Center for Translational Science Activities, Mayo Clinic, Rochester, MN, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
authors.affiliation: Department of Physiology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: I J
authors.initials: IJ
authors.lastname: Clarke
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Anderson
authors.affiliation: Department of Medical Biochemistry and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.|Mammal Research Institute and Centre for Neuroendocrinology, University of Pretoria, Pretoria, South Africa.
authors.forename: R P
authors.initials: RP
authors.lastname: Millar
mesh_terms: D005260:Female; D006801:Humans; D059648:Kisspeptins / Q000008:administration & dosage / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D017698:Postmenopause / Q000378:metabolism
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D009479:Neuropeptides; C416987:RFamide peptide; D007986:Luteinizing Hormone