The Reproductive Physiology of Leptin

Abstract

Leptin is a 16kDa protein hormone thought to regulate energy homeostasis and circulates at levels corresponding to fat mass and acute changes in the nutritional status. Leptin has been proposed as a metabolic mediator linking nutritional status with the reproductive axis in mammals and leptin receptors have been identified in hypothalamic areas regulating feeding behavior and reproductive processes. Leptin may be involved in indicating the reproductive system that adequate energy stores are available for normal reproductive functions. In addition, leptin has been shown to regulate maturation of the reproductive system, gonadotropin secretion, onset of puberty, gonadal function, embryonic development and implantation, fetal development, pregnancy and parturition. Recent studies have shown that low levels of leptin exert a stimulatory effect on the reproductive system whereas higher levels are inhibitory. This biphasic effect of leptin has been demonstrated in number of physiological systems. To further confirm this hypothesis, the present thesis was aimed to study effect of leptin on female reproduction following lowering/neutralization of leptin levels in the circulation or blocking its action in vivo. In this thesis, it is reported for the first time that administration of anti-leptin or anti-leptin receptor antiserum in vivo exerts significant positive effects on various reproductive processes in female mice including ovarian follicular development, ovulation, embryonic implantation and pregnancy. These results provide new evidence that leptin signaling plays multiple important roles in mouse reproduction.