Leptin accelerates the onset of puberty in normal female mice.

TLDR

Leptin, a fat‑derived hormone, signals the brain to reduce food intake and body weight, restores puberty and fertility in leptin‑deficient mice, and may link adiposity to reproduction. The study examined whether daily recombinant leptin injections would advance puberty onset in weaned female mice fed ad libitum, given the role of adiposity and rising leptin levels in pubertal timing. Leptin is proposed to inform the brain that energy stores are sufficient to support reproduction, potentially determining pubertal timing. Leptin injections accelerated puberty, causing earlier vaginal opening, estrus, and cycling while body weight rose linearly regardless of dose, demonstrating leptin as the first peripheral molecule to accelerate reproductive maturation in normal rodents.

Abstract

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.