A signaling role for leptin in puberty onset in female rats?

The brain might initiate puberty in response to adequate leptin signaling from the periphery. We studied the link between whole body fat, plasma leptin levels, and puberty onset, in both controls and food-restricted female Wistar rats from age 22 to 42 days. Body fat correlated positively with the prevailing plasma leptin levels (r = 0.776) and with the time of puberty onset, i.e. vaginal opening (VO) (r = 0.691). Blood samples collected every other day at ZT 2, 6, and 12, showed a diurnal rhythm in leptin levels with a nadir at ZT 6. Furthermore, leptin levels increased over the pubertal period. Food restriction (FR) delayed the time of VO considerably (median VO at 38 vs 28 d), and body fat and plasma leptin levels were lower in the FR group (p <0.01), although the positive correlation between body fat and leptin levels remained. Only the absolute, but not the relative amount of body fat increased with age. These data support the notion that leptin could indeed serve as the link between nutritional status and the reproductive axis, and in this way participate in the timing of puberty.

Central application of IGF-1 postpones time of vaginal opening in normally fed, but not in food-restricted rats.

BACKGROUND/AIMS: Central but also peripheral IGF-1 is suggested to play a role in the initiation of puberty as it directly affects GnRH synthesis and release. A possible intermediate in the effects of IGF-1 on puberty might be the adiposity-signaling hormone leptin, whose plasma levels are decreased in food-restricted (FR) rats. METHODS: IGF-1 was chronically centrally infused in 23-day-old prepubertal female rats which were either normally fed or 30% FR, and the effects on time of vaginal opening (VO) and plasma leptin levels were monitored. RESULTS: FR treatment postponed time of VO and decreased plasma leptin levels. In normally fed rats centrally infused with IGF-1, time of VO was found to be postponed to the same extent as FR treatment did. The IGF-1 infusion did not affect plasma leptin levels in normally fed animals but increased leptin levels in the FR group compared to controls. Daily food intake was equal between all groups but body weight course was lower in FR rats. IGF-1 treatment did not significantly affect food intake or body weight course. CONCLUSION: FR treatment delays the moment of vaginal opening to the same extent as observed in normally fed rats that were centrally infused with IGF-1.

Chronic leptin infusion advances, and immunoneutralization of leptin postpones puberty onset in normally fed and feed restricted female rats.

Does leptin play a vital role in initiating puberty in female rats and can it overrule a nutrionally imposed (i.e. a 30% feed restriction, FR) delay in puberty onset? Prepubertal female rats were chronically infused for 14 days with leptin (icv or sc) or leptin-antiserum (icv) while puberty onset was monitored by means of scoring the moment of vaginal opening (VO). Median VO age was higher (35 days versus 27 days) in FR animals but leptin levels at VO were significantly decreased (1.44 +/- 0.17 ng/ml versus 2.79 +/- 0.31 ng/ml). Centrally (icv) and peripherally (sc) infused leptin (1 microg/day) advanced VO age compared to FR controls (30 days versus 35 days and 31 days versus 41 days, respectively). Congruently, centrally (icv) administered leptin-antiserum (0.6 microg/day) delayed puberty onset. In normally fed rats median VO age was only marginally advanced (26 days versus 27 days) but only if leptin was applied centrally. The effects of FR on puberty onset are counteracted or even normalized by the infusion of leptin, whereas immunoneutralization of central leptin postpones puberty onset. We therefore conclude that central leptin is crucial for initiating puberty in female rats.