Roberts Stephanie A, Abreu Ana Paula, Navarro Victor M, Liang Joy N, Maguire Caroline A, Kim Han Kyeol, Carroll Rona S, Kaiser Ursula B
Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts.
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts.
J Endocr Soc. 2020 May 21;4(7):bvaa059. doi: 10.1210/jendso/bvaa059. eCollection 2020 Jul 1.
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.
临界体重对于青春期发育是必要的，这一作用部分由瘦素介导。瘦素对[基因名称未给出]的潜在调节作用此前尚未被探索，而该基因功能丧失突变是中枢性性早熟最常见的遗传原因。在小鼠中，[基因名称未给出]在下丘脑弓状核的表达在生命早期较高，并在青春期开始前下降。因此，我们旨在探讨瘦素是否导致了在青春期发育期间小鼠下丘脑[基因名称未给出]mRNA水平的下降。我们首先使用了瘦素缺乏（[具体基因符号未给出]）小鼠模型。在包括弓状核的中基底下丘脑（MBH）以及视前区（POA）中，[基因名称未给出]mRNA水平在雄性和雌性[基因名称未给出]小鼠中从出生后第12天（PND）到PND30均随年龄显著下降，与野生型小鼠中观察到的情况相似。为了进一步探究瘦素对[基因名称未给出]表达的影响，我们在PND9 - 12期间将青春期前的野生型小鼠暴露于高水平的瘦素中，这并未导致MBH或POA中[基因名称未给出]表达水平出现任何显著差异。总之，在对青春期成熟很重要的两个下丘脑部位MBH和POA中均未观察到瘦素对[基因名称未给出]表达的调节作用。这些数据表明青春期开始时[基因名称未给出]的下降可能独立于瘦素发生，并支持了我们的假设，即MKRN3是青春期启动的真正调控因子。
