title: Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men.
abstract: BACKGROUND
  Kisspeptins stimulate GnRH and thus gonadotropin secretion. Kisspeptin-10 is the minimal kisspeptin sequence with full intrinsic bioactivity, but it has not been studied in man.
  
  
  OBJECTIVE
  We investigated our hypothesis that kisspeptin-10 increases GnRH and thus LH pulse frequency.
  
  
  METHODS
  The dose response of kisspeptin-10 was investigated by administering iv bolus doses (0.01-3.0 μg/kg) and vehicle to healthy men. Effects on LH pulse frequency and size were determined by deconvolution analysis during infusion of kisspeptin-10 for up to 22.5 h.
  
  
  RESULTS
  Intravenous bolus kisspeptin-10 resulted in a rapid and dose-dependent rise in serum LH concentration, with maximal stimulation at 1 μg/kg (4.1 ± 0.4 to 12.4 ± 1.7 IU/liter at 30 min, P < 0.001, n = 6). Administration of 3 μg/kg elicited a reduced response vs. 1 μg/kg (P < 0.05). Infusion of kisspeptin-10 at 4 μg/kg · h for 22.5 h elicited an increase in LH from a mean of 5.4 ± 0.7 to 20.8 ± 4.9 IU/liter (n = 4; P < 0.05) and serum testosterone increased from 16.6 ± 2.4 to 24.0 ± 2.5 nmol/liter (P < 0.001). LH pulses were obscured at this high rate of secretion, but a lower dose infusion of kisspeptin-10 (1.5 μg/kg · h) increased mean LH from 5.2 ± 0.8 to 14.1 ± 1.7 IU/liter (n = 4; P < 0.01) and increased LH pulse frequency from 0.7 ± 0.1 to 1.0 ± 0.2 pulses/h (P < 0.05) and secretory burst mass from 3.9 ± 0.4 to 12.8 ± 2.6 IU/liter (P < 0.05).
  
  
  CONCLUSIONS
  Kisspeptin-10 boluses potently evoke LH secretion in men, and continuous infusion increases testosterone, LH pulse frequency, and pulse size. Kisspeptin analogues have therapeutic potential as regulators of LH and thus testosterone secretion.
authors.affiliation: Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK. j.george@ed.ac.uk
authors.forename: J T
authors.initials: JT
authors.lastname: George
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: A K
authors.initials: AK
authors.lastname: Roseweir
authors.forename: C L
authors.initials: CL
authors.lastname: Newton
authors.forename: E
authors.initials: E
authors.lastname: Faccenda
authors.forename: R P
authors.initials: RP
authors.lastname: Millar
authors.forename: R A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000097:blood / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism*; D007275:Injections, Intravenous; D059648:Kisspeptins; D007986:Luteinizing Hormone / Q000097:blood* / Q000378:metabolism*; D008297:Male; D013618:Tachyphylaxis; D013739:Testosterone / Q000097:blood / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000008:administration & dosage*
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone