Korean J Pediatr.
2012 Sep;55(9):337-343. 10.3345/kjp.2012.55.9.337.
Excess of leptin inhibits hypothalamic KiSS-1 expression in pubertal mice
- Affiliations
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- 1Department of Pediatrics, Kangwon National University School of Medicine, Chuncheon, Korea.
- 2Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea. chshinpd@snu.ac.kr
- 3Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon, Korea.
- KMID: 2284392
- DOI: http://doi.org/10.3345/kjp.2012.55.9.337
Abstract
- 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 microg) 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-microg 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-LH-estradiol feedback loop.
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