Leptin accelerates the onset of puberty in normal female mice
Leptin accelerates the onset of puberty in normal female mice
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DOI：
10.1172/jci119172
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发表时间：
1997-02-01
影响因子：
15.9
通讯作者：
Flier, JS
中科院分区：
文献类型：
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作者：
Ahima, RS;Dushay, J;Flier, JS
脂肪衍生的激素，瘦素，被认为是大脑的脂肪抑制信号，以减少食物摄入和体重。除了其对体重的影响，长期瘦素治疗恢复青春期和生育能力的ob/ob小鼠与总瘦素缺乏症，和急性治疗基本上纠正性腺功能减退症饥饿2天的小鼠不影响体重。因此，瘦素可能是一个关键的信号，连接肥胖和生殖。由于体重和肥胖似乎在人类和啮齿动物的青春期时间中起着关键作用，瘦素水平随着肥胖的增加而升高，我们研究了每天一次注射重组瘦素对第21天断奶并随意喂养的雌性小鼠青春期开始的影响。在研究期间，体重呈线性增加，但不受瘦素剂量的影响。注射瘦素的小鼠具有三个经典青春期参数的早期发作（即，阴道开口、发情和周期）与盐水注射对照相比。瘦素是第一个被证实能加速正常啮齿类动物生殖轴成熟的外周分子。我们认为，瘦素是一种信号，告知大脑能量储存足以支持生殖的高能量需求，并可能是青春期时间的主要决定因素。
The fat-derived hormone, leptin, is proposed to serve as an adipostatic signal to the brain to reduce food intake and body weight. In addition to its effects on body weight, chronic leptin treatment restores puberty and fertility to ob/ob mice with total leptin deficiency, and acute treatment substantially corrects hypogonadism in mice starved for 2 d without affecting body weight. Leptin may therefore be a critical signal, linking adiposity and reproduction. Since body weight and adiposity appear to play a critical role in the timing of puberty in humans and rodents, and leptin levels rise with increasing adiposity, we studied the effects of once daily injections of recombinant leptin on the onset of puberty in female mice weaned on day 21 and fed ad libitum. There was a linear increase in body weight during the study period, which was not altered by the dose of leptin used. Mice injected with leptin had an earlier onset of three classic pubertal parameters (i.e., vaginal opening, estrus, and cycling) compared with saline-injected controls. Leptin is the first peripheral molecule demonstrated to accelerate the maturation of the reproductive axis in normal rodents. We propose that leptin is the signal that informs the brain that energy stores are sufficient to support the high energy demands of reproduction, and may be a major determinant of the timing of puberty.