Cheung C C, Thornton J E, Kuijper J L, Weigle D S, Clifton D K, Steiner R A
Department of Physiology & Biophysics, University of Washington, Seattle 98195-6460, USA.
Endocrinology. 1997 Feb;138(2):855-8. doi: 10.1210/endo.138.2.5054.
The timing of puberty onset in mammals is tightly coupled to the animal's nutritional and metabolic state. We conducted two experiments to test the hypothesis that leptin acts as a metabolic signal for the onset of puberty. In the first experiment, we administered leptin (6.3 micrograms/g twice daily) to a group of normal prepubertal female rats and compared their rate of sexual maturation to that of two control groups. The group of leptin-treated animals and one group of control animals were allowed to eat ad lib, while the other group of control animals was pair-fed to the leptin-treated group. Food intake in the leptin-treated group was reduced to approximately 80% of the ad lib-fed control group, resulting in retarded growth in both leptin-treated and pair-fed animals. All measured indices of pubertal maturation-age at vaginal opening, age at first estrus, ovarian weight, ovulatory index (corpora lutea/ovarian section), uterine weight, and uterine cross-sectional area-were significantly delayed in the pair-fed group but not different between the leptin-treated group and ad lib-fed controls. The second experiment was similar to the first, except that both the leptin-treated group and the pair-fed group were fed at 70% of the ad lib-fed controls. Under these conditions, leptin only partially reversed the delay in sexual maturation, as reflected by the age at vaginal opening and first estrus. These results suggest that leptin is not the primary signal that initiates the onset of puberty but that instead, it acts in a permissive fashion, as a metabolic gate, to allow pubertal maturation to proceed-if and when metabolic resources are deemed adequate; moreover, these observations suggest that other metabolic factors, besides leptin, influence the timing of puberty onset under conditions of more severe dietary stress.
哺乳动物青春期开始的时间与动物的营养和代谢状态紧密相关。我们进行了两项实验来验证瘦素作为青春期开始的代谢信号这一假说。在第一个实验中，我们给一组正常的青春期前雌性大鼠注射瘦素（6.3微克/克，每日两次），并将它们的性成熟速率与两个对照组进行比较。给注射瘦素的动物组和一组对照组随意进食，而另一组对照组则与注射瘦素的组进行配对喂食。注射瘦素组的食物摄入量减少到随意进食对照组的约80%，导致注射瘦素组和配对喂食组的生长都受到抑制。所有测量的青春期成熟指标——阴道开口年龄、首次发情年龄、卵巢重量、排卵指数（黄体数/卵巢切片）、子宫重量和子宫横截面积——在配对喂食组中均显著延迟，但在注射瘦素组和随意进食对照组之间没有差异。第二个实验与第一个实验相似，只是注射瘦素组和配对喂食组都按随意进食对照组的70%喂食。在这些条件下，瘦素仅部分逆转了性成熟的延迟，这通过阴道开口年龄和首次发情年龄得以体现。这些结果表明，瘦素不是启动青春期开始的主要信号，而是以一种允许的方式起作用，作为一个代谢闸门，在代谢资源被认为充足时允许青春期成熟进行；此外，这些观察结果表明，除了瘦素之外，其他代谢因素在更严重的饮食压力条件下会影响青春期开始的时间。
