産婦人科領域におけるレプチンの意義

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Leptin is an adipocyte-derived hormone that is involved in the regulation of food intake and energy expenditure. Short-term administration of leptin accelerates the onset of puberty in normal mice and corrects the sterility of leptin-deficient ob/ob mice. These findings suggest a putative role of leptin as an endocrine signal between fat depots and the reproductive axis. However, the effect of hyperleptinemia on the initiation and maintenance of reproductive function has not been elucidated. To address this issue, we examined the reproductive phenotypes of female transgenic skinny mice(Tg-mice)with elevated plasma leptin concentrations comparable to those in obese subjects. With no apparent adipose tissue, female Tg-mice exhibit accelerated puberty and intact fertility at younger ages followed by successful delivery of healthy pups. However, at older ages, they develop hypothalamic hypogonadism characterized by prolonged menstrual cycles, atrophic ovary, reduced hypothalamic gonadotropin releasing hormone(GnRH)contents and poor pituitary luteinizing hormone secretion. This study has demonstrated for the first time that accelerated puberty and late onset hypothalamic hypogonadism are associated with chronic hyperleptinemia. In the present study, we demonstrated that leptin is produced by placental trophoblasts and amnion cells and is secreted into both maternal and fetal circulations during human pregnancy. We also examined immunohistochemical localization of leptin and obese gene expression in molar tissues in 7 women with hydatidiform mole. Immunohistochemically, trophoblast cells were clearly stained for leptin. Northern blot analysis demonstrated augmented obese gene expression in molar tissue. Intrauterine growth retardation(IUGR)of the fetus due to placental hypoperfusion is one of the most common complications in preeclampsia. In this study, we compared the maternal plasma leptin levels with maternal mean blood pressure and degree of fetal growth restriction. Plasma leptin levels were correlated well with mean blood pressure, but not with body mass index(BMI). plasma leptin levels in preeclamptic women with IUGR were significantly elevated, compared to those without IUGR(p<0.05). Moreover plasma leptin levels were negatively correlated with relative birth weight(*△SD). These dada suggest the possibility that maternal plasma leptin may be useful as a clinical marker of maternal hypertension as well as fetal growth restriction. The present study provides the first evidence for leptin as a novel placenta-derived hormone in humans and suggests the physiologic and pathophysiologic significance of leptin in normal and abnormal pregnancy.
社団法人日本産科婦人科学会の論文
2001-09-01

産婦人科領域におけるレプチンの意義

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