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.