CHRONIC ADMINISTRATION OF LEPTIN INTO THE LATERAL VENTRICLE INDUCES SEXUAL-MATURATION IN SEVERELY FOOD-RESTRICTED FEMALE RATS

In many species, delayed sexual maturation occurs when metabolic condi tions are not satisfactory. Recently, leptin was shown to be involved in the regulation of food intake and body mass. Furthermore, leptin ad ministration was shown to advance sexual maturation in mice and to res cue sexual function in adverse metabolic conditions, We examined plasm a leptin levels in female rats during development and evaluated the ro le of leptin on sexual maturation in rats subjected to food restrictio n. In normal rats, plasma leptin levels were low at day 24 of life, th en steadily increased during the juvenile period, reaching 740 +/- 56 pg/ml at 40 days at time of vaginal opening (VO) and further increasin g by day 60 (957 +/- 73 pg/ml). Food restriction initiated at day 25 s trongly impaired this increase, in proportion to the severity of the r estriction. With a daily food intake reduced to 7-8 g/day, that perman ently prevented VO, plasma leptin levels were very low at day 53 (169 +/- 67 pg/ml). Following switch to ad libitum feeding, plasma leptin r eached high levels within 2 days (1577 +/- 123 pg/ml), and VO occurred 4 days later. If the severe food restriction was maintained and a cen tral infusion of leptin (10 mu g/day) was initiated, a significant dec rease in body weight compared with vehicle-infused controls was observ ed. In these conditions, VO occurred in eight out of the nine leptin-t reated rats, representing induction of the process of sexual maturatio n confirmed by increases in ovarian and uterine weights. This inductio n of sexual maturation exclusively results from a central effect of le ptin because no leak of the icy administered leptin to the general cir culation was observed. These data suggest that the rising plasma level s of leptin in the prepubertal period represent a signal to the brain indicating that the young animal is metabolically ready to go through the process of sexual maturation.