title: Kisspeptin resets the hypothalamic GnRH clock in men.
abstract: BACKGROUND
  Reproduction in all mammals is controlled by a hypothalamic clock that produces periodic secretory pulses of GnRH, but how the timing of these pulses is determined is poorly understood. The neuropeptide kisspeptin potently and selectively stimulates the secretion of GnRH. Although this property of kisspeptin is well described, the effects of kisspeptin on endogenous GnRH pulse generation remain largely unexplored.
  
  
  OBJECTIVE
  The objective of the study was to detail the effects of kisspeptin on GnRH secretion, as reflected by LH secretion, in men.
  
  
  METHODS
  Thirteen healthy adult men participated in the study.
  
  
  METHODS
  The intervention was the administration of a single iv bolus of the C-terminal decapeptide of kisspeptin (amino acids 112-121 of the parent protein).
  
  
  RESULTS
  Kisspeptin induced an immediate LH pulse, regardless of the timing of the previous endogenous pulse. The kisspeptin-induced pulses were on average larger than endogenous pulses (amplitude 5.0 ± 1.0 vs. 2.1 ± 0.3 mIU/ml, P = 0.02). Comparison of the morphology of kisspeptin-induced LH pulses in healthy men with that of GnRH-induced LH pulses in men with isolated GnRH deficiency suggests that a single i.v. bolus of kisspeptin triggered sustained GnRH release lasting approximately 17 min. Furthermore, kisspeptin reset the GnRH pulse generator, as it not only induced an immediate LH pulse but also delayed the next endogenous pulse by an interval approximating the normal interpulse interval.
  
  
  CONCLUSIONS
  As the first known agent capable of resetting the hypothalamic GnRH pulse generator, kisspeptin can be used as a physiological tool for studying GnRH pulse generation and opens a door to understanding the mechanisms of biological clocks in general.
authors.affiliation: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, BHX 5, Boston, Massachusetts 02114, USA. ymchan@partners.org
authors.forename: Yee-Ming
authors.initials: YM
authors.lastname: Chan
authors.forename: James P
authors.initials: JP
authors.lastname: Butler
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Pinnell
authors.forename: François P
authors.initials: FP
authors.lastname: Pralong
authors.forename: William F
authors.initials: WF
authors.lastname: Crowley
authors.forename: Chen
authors.initials: C
authors.lastname: Ren
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Chan
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Seminara
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects*; D059648:Kisspeptins; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D010507:Periodicity; D025521:Tumor Suppressor Proteins / Q000494:pharmacology*
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone