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Korean J Pediatr 2012 September;55(9) :337-343.
Published online 2012 September 14.        doi:
Excess of leptin inhibits hypothalamic KiSS-1 expression in pubertal mice
Sung Yeon Ahn (Ahn SY)1, Sei Won Yang (Yang SW)2, Hee Jae Lee (Lee HJ)3, Jong Seon Byun (Byun JS)3, Ji Yeon Om (Om JY)3, Choong Ho Shin (Shin CH)2
1Department of Pediatrics, Kangwon National University School of Medicine, Chuncheon, Korea
2Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
3Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon, Korea
Corresponding Author: Choong Ho Shin ,Tel: +82-2-2072-3357, Fax: +82-2-743-3455, Email:
Copyright © 2012 by The Korean Pediatric Society
Purpose: 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 g) 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-g 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. Conclusion: 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-LHestradiol feedback loop.
Keywords: Leptin | KiSS-1 | Gonadotropin-releasing hormone | Luteinizing hormone | Puberty
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