LEPTIN ACCELERATES THE ONSET OF PUBERTY IN NORMAL FEMALE MICE

The fat-derived hormone, leptin, is proposed to serve as an adipostati c signal to the brain to reduce food intake and body weight. In additi on to its effects on body weight, chronic leptin treatment restores pu berty and fertility to ob/ob mice with total leptin deficiency, and ac ute 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 adip osity appear to play a critical role in the timing of puberty in human s and rodents, and leptin levels rise with increasing adiposity, we st udied the effects of once daily injections of recombinant leptin on th e 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, w hich was not altered by the dose of leptin used. Mice injected with le ptin had an earlier onset of three classic pubertal parameters (i.e., vaginal opening, estrus, and cycling) compared with saline-injected co ntrols. Leptin is the first peripheral molecule demonstrated to accele rate the maturation of the reproductive axis in normal rodents. We pro pose that leptin is the signal that informs the brain that energy stor es are sufficient to support the high energy demands of reproduction, and may be a major determinant of the timing of puberty.