Leptin in reproduction.
OBJECTIVE
Leptin, a key hormone in energy homeostasis and neuroendocrine function, has a permissive role in initiating puberty and is crucial in the pathogenesis of reproductive dysfunction in several disease states of energy imbalance. KiSS1 neurons have recently been suggested to mediate leptin's effect on the reproductive system. New insights from recent animal studies and clinical trials are discussed.


RESULTS
Alterations in the expression profile of the KiSS1 gene and the kisspeptin receptor have been linked to reproductive dysfunction in leptin-deficient states. Neuroendocrine, including reproductive, dysfunction can be restored in humans and animals by leptin-replacement therapy. These insights have significantly advanced our understanding of hormonal systems needed to maintain normal reproduction. These data, if confirmed, also suggest a role for leptin as a novel therapeutic approach in several disease states.


CONCLUSIONS
Recent proof-of-concept studies involving leptin administration to humans underline the critical role of leptin not only in regulating energy homeostasis, but also in maintaining normal reproductive function. Leptin-replacement therapy is currently under intensive investigation as a potential novel therapeutic option for several conditions associated with reproductive dysfunction due to hypoleptinemia.
Blüher
Susann
S
Children's Hospital, University of Leipzig, Leipzig, Germany.
Mantzoros
Christos S
CS
D000568:Amenorrhea / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000856:Anorexia Nervosa / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D004734:Energy Metabolism; D005260:Female; D006066:Gonads / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000503:physiopathology; D007246:Infertility / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D059648:Kisspeptins; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008572:Menarche / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D011627:Puberty / Q000378:metabolism; D012098:Reproduction; D012727:Sex Characteristics; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C106628:KISS1 protein, human; D059648:Kisspeptins; D020738:Leptin; D025521:Tumor Suppressor Proteins