Leptin, nutrition and reproduction: new insights

Recent data suggest that in addition to leptin's role in conveying signals of the amount of energy stores to the central nervous system, this adipocyte secreted hormone interacts with the endocrine system to provide critical information about the size of fat stores, acting as a permissive factor that allows the triggering of energy demanding situations as the onset of puberty and reproduction. Animal and human data are concordant with the concept that leptin plays an important permissive role in the initiation of puberty and in maintenance of reproductive function thereafter. Leptin regulates the gonadotropin-gonadal axis at a central level. The hypothalamus is an important site of leptin's action where a complex network of neuropeptides is involved in leptin's effect on GnRH. In addition, leptin plays a role during pregnancy and lactation as it is produced by the placenta and is present in milk. Plasma leptin levels are elevated during pregnancy and this hyperleptinemia is not accompanied by a reduction in food intake, suggesting a state of leptin resistance. Leptin is also detected in the amniotic fluid and its levels are high in venous cord blood at delivery correlating positively with weight at birth which suggests a potential role in intrauterine growth. The fact that in females leptin levels are higher than in males, even when corrected for body fat, suggests that the reproductive system is modulated by leptin in a different way in males and females estrogens. In hypoleptinemia resulting from specific genetic causes, leptin levels may still be adequate for the function of the reproductive system in humans, a phenomenon which differs from the findings in leptin-deficient animals which are infertile. Due to species differences in the role of leptin, it is difficult to extrapolate data from rodents to human physiology. However hypoleptinemia due to non-genetic causes such as anorexia nervosa and exercise leads to loss of reproductive function. Genetic/developmental factors influence the threshold required to turn off the behavioral, metabolic and endocrine responses to perceived caloric deprivation.