LEPTIN IS A METABOLIC GATE FOR THE ONSET OF PUBERTY IN THE FEMALE RAT

The timing of puberty onset in mammals is tightly coupled to the anima l's nutritional and metabolic state. We conducted two experiments to t est the hypothesis that leptin acts as a metabolic signal for the onse t of puberty. In the first experiment, we administered leptin (6.3 mu g/g twice daily) to a group of normal prepubertal female rats and comp ared their rate of sexual maturation to that of two control groups. Th e group of leptin-treated animals and one group of control animals wer e allowed to eat ad iib, while the other group of control animals was pair-fed to the leptin-treated group. Food intake in the leptin-treate d group was reduced to approximately 80% of the ad Iib-fed control gro up, resulting in retarded growth in both leptin-treated and pair-fed a nimals. All measured indices of pubertal maturation-age at vaginal ope ning, age at first estrus, ovarian weight, ovulatory index (corpora lu tea/ovarian section), uterine weight, and uterine cross-sectional area -were significantly delayed in the pair-fed group but not different be tween the leptin-treated group and ad lib-fed controls. The second exp eriment 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 control s. Under these conditions, leptin only partially reversed the delay in sexual maturation, as reflected by the age at vaginal opening and fir st estrus. These results suggest that leptin is not the primary signal that initiates the onset of puberty but that instead, it acts in a pe rmissive 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 lep tin, influence the timing of puberty onset under conditions of more se vere dietary stress.