Zhao J, Townsend K L, Schulz L C, Kunz T H, Li C, Widmaier E P
Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
Placenta. 2004 Sep-Oct;25(8-9):712-22. doi: 10.1016/j.placenta.2004.01.017.
In addition to effects on appetite and metabolism, the hormone leptin is required for reproduction in mammals. Maternal plasma leptin is increased above non-pregnant levels in all mammals thus far examined, including humans. The increase in plasma leptin appears to result in part from upregulation of adipose leptin secretion (e.g., in mice), or from production and secretion of leptin from the placenta (e.g., in humans and some bats). The placenta may also modulate maternal leptin levels via production of a plasma leptin-binding protein (mice, humans). Thus, the placenta plays a coordinating role in regulation of maternal leptin during pregnancy. In this study, the hypothesis that the placenta is also a target organ for leptin in diverse taxa was tested by examining the expression of leptin receptors (Ob-R) in placentae from species of distantly related mammalian taxa, Mus musculus (the laboratory mouse) and Myotis lucifugus (the little brown myotis, also called the little brown bat). A partial sequence of M. lucifugus Ob-R cDNA was first obtained and found to share approximately 78-88% homology at the nucleotide level with known mammalian Ob-R cDNAs. Using probes and primers designed from this sequence, receptor expression was detected in numerous tissues of M. lucifugus, including placenta, which expressed two major receptor isoforms as judged by molecular size. In both species, Ob-R mRNA expression in placenta significantly increased from early to late gestation. Expression of Ob-R mRNA was not affected by cAMP treatment in vitro. The increase in Ob-R mRNA expression in placenta was specific, since Ob-R mRNA expression did not change during gestation in either species in hypothalamus, the major site of the central actions of leptin. Thus, Ob-R is expressed in placenta throughout gestation in mice and bats, and its expression increases over the course of gestation, which raises the possibility that leptin may exert temporally distinct effects on placental growth or function throughout gestation. Because similar placenta-specific changes in leptin receptor expression occurred in species from distantly related mammalian taxa which collectively comprise approximately 70% of all known mammalian species, it is possible that placental actions of leptin are conserved across mammals, even in those species (such as the Swiss-Webster strain of mouse) in which the placenta does not itself produce leptin.
除了对食欲和新陈代谢有影响外,激素瘦素对哺乳动物的繁殖也是必需的。在包括人类在内的迄今为止所研究的所有哺乳动物中,母体血浆中的瘦素水平均高于非孕期水平。血浆瘦素水平的升高部分似乎是由于脂肪组织中瘦素分泌上调(如在小鼠中),或胎盘产生并分泌瘦素(如在人类和一些蝙蝠中)。胎盘还可能通过产生血浆瘦素结合蛋白来调节母体瘦素水平(小鼠、人类)。因此,胎盘在孕期母体瘦素的调节中发挥着协调作用。在本研究中,通过检测远缘相关哺乳动物类群小家鼠(实验小鼠)和小棕蝠(也称为棕色小蝙蝠)胎盘组织中瘦素受体(Ob-R)的表达,来验证胎盘也是不同类群中瘦素靶器官这一假说。首先获得了小棕蝠Ob-R cDNA的部分序列,发现其在核苷酸水平上与已知哺乳动物Ob-R cDNA具有约78%-88%的同源性。利用根据该序列设计的探针和引物,在小棕蝠的许多组织中检测到了受体表达,包括胎盘,根据分子大小判断,胎盘表达两种主要的受体异构体。在这两个物种中,胎盘组织中Ob-R mRNA的表达从妊娠早期到晚期均显著增加。体外cAMP处理对胎盘组织中Ob-R mRNA的表达没有影响。胎盘组织中Ob-R mRNA表达的增加具有特异性,因为在瘦素发挥中枢作用的主要部位下丘脑,这两个物种在孕期Ob-R mRNA的表达均未发生变化。因此,Ob-R在小鼠和蝙蝠整个孕期的胎盘中均有表达,且其表达在孕期过程中增加,这增加了瘦素可能在整个孕期对胎盘生长或功能产生不同时间效应的可能性。由于在远缘相关哺乳动物类群的物种中出现了类似的胎盘特异性瘦素受体表达变化,这些类群共同构成了所有已知哺乳动物物种的约70%,因此即使在胎盘本身不产生瘦素的物种(如瑞士-韦伯斯特品系小鼠)中,瘦素的胎盘作用在哺乳动物中也可能是保守的。