title: Excess of leptin inhibits hypothalamic KiSS-1 expression in pubertal mice.
abstract: OBJECTIVE
  Leptin has been considered a link between metabolic state and reproductive activity. Defective reproductive function can occur in leptin-deficient and leptin-excessive conditions. The aim of this study was to examine the effects of centrally injected leptin on the hypothalamic KiSS-1 system in relation to gonadotropin-releasing hormone (GnRH) action in the initial stage of puberty.
  
  
  METHODS
  Leptin (1 µg) was injected directly into the ventricle of pubertal female mice. The resultant gene expressions of hypothalamic GnRH and KiSS-1 and pituitary LH, 2 and 4 hours after injection, were compared with those of saline-injected control mice. The changes in the gene expressions after blocking the GnRH action were also analyzed.
  
  
  RESULTS
  The basal expression levels of KiSS-1, GnRH, and LH were significantly higher in the pubertal mice than in the prepubertal mice. The 1-µg leptin dose significantly decreased the mRNA expression levels of KiSS-1, GnRH, and LH in the pubertal mice. A GnRH antagonist significantly increased the KiSS-1 and GnRH mRNA expression levels, and the additional leptin injection decreased the gene expression levels compared with those in the control group.
  
  
  CONCLUSIONS
  The excess leptin might have suppressed the central reproductive axis in the pubertal mice by inhibiting the KiSS-1 expression, and this mechanism is independent of the GnRH-LH-estradiol feedback loop.
authors.affiliation: Department of Pediatrics, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Sung Yeon
authors.initials: SY
authors.lastname: Ahn
authors.forename: Sei Won
authors.initials: SW
authors.lastname: Yang
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jong Seon
authors.initials: JS
authors.lastname: Byun
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Om
authors.forename: Choong Ho
authors.initials: CH
authors.lastname: Shin