The Peripubertal Decline in Expression is Independent of Leptin Action.

A critical body weight is necessary for pubertal development, an effect mediated in part by leptin. The potential regulation by leptin of , in which loss-of-function mutations are the most common genetic cause of central precocious puberty, has not been previously explored. In mice, expression of in the hypothalamic arcuate nucleus is high early in life and declines before the onset of puberty. Therefore, we aimed to explore if leptin contributes to the decrease in hypothalamic mRNA levels observed in mice during pubertal development. We first used a leptin-deficient () mouse model. mRNA levels in the mediobasal hypothalamus (MBH), which includes the arcuate nucleus, and in the preoptic area (POA), both showed a significant decrease with age from postnatal day (PND) 12 to PND30 in mice in both males and females, similar to that observed in wild-type mice. To further explore the effects of leptin on expression, we exposed prepubertal wild-type mice to high levels of leptin from age PND9-12, which did not result in any significant difference in expression levels in either the MBH or POA. In summary, regulation of expression by leptin was not observed in either the MBH or the POA, 2 hypothalamic sites important for pubertal maturation. These data suggest that the decline in at the onset of puberty may occur independently of leptin and support our hypothesis that MKRN3 is a bona fide controller of puberty initiation.