No Kiss1ng by leptin during puberty?
Rexford S. Ahima
Rexford S. Ahima
Published December 22, 2010
Citation Information: J Clin Invest. 2011;121(1):34-36. https://doi.org/10.1172/JCI45813.
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Commentary

No Kiss1ng by leptin during puberty?

Abstract

Leptin exerts a permissive action on puberty by stimulating release of gonadotropin-releasing hormone (GnRH) in the hypothalamus. However, GnRH neurons lack leptin receptor (LepR), indicating that leptin must indirectly regulate these neurons. The Kiss1 gene produces kisspeptins that stimulate GnRH secretion. Because Kiss1 neurons express LepR and inactivation of Kiss1 causes hypogonadotropic hypogonadism, Donato et al., in this issue of the JCI, assessed whether deletion of LepR from Kiss1 neurons would prevent sexual maturation. Unexpectedly, mice lacking LepR in Kiss1 neurons had normal pubertal development and fertility. In contrast, deletion of LepR from the ventral premammillary nucleus, a region of the brain involved in sexual behavior, prevented puberty and fertility. These findings highlight the complex biology of leptin in reproduction.

Authors

Rexford S. Ahima

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Figure 1

Schematic representation of Kiss1 and leptin signaling in mouse brain.

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Schematic representation of Kiss1 and leptin signaling in mouse brain. K...
Kisspeptins are expressed by Kiss1 neurons in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (Arc), which innervate GnRH neurons. Sex steroids (estradiol and testosterone) exert feedback regulation on Kiss1 levels. At the onset of puberty, the sex steroids exert positive feedback regulation of Kiss1, increasing GnRH release into the pituitary portal circulation and thereby stimulating the secretion of gonadotropins and sex steroids as well as reproductive maturation. As indicated by the work of Donato et al. (12), although Kiss1 neurons express LepR, targeted deletion of Lepr in these neurons does not have an impact on puberty. Rather, leptin acts directly on the PMV and increases GnRH secretion through glutaminergic neurotransmission (12).