Abstract：
The purpose of this study was to determine the receptor subtype and the underlying mechanisms involved in the relaxant effect to leptin in mid- and late-pregnant mouse uterus. We determined the relative mRNA expression of receptor subtypes, eNOS, and BKCa channel by quantitative PCR and also the overall receptor expression by immunohistochemistry. Isometric tension studies were conducted to evaluate the effects of leptin and to delineate its mechanisms. A selective siRNA for the ObRb receptor was used to determine the participation of the receptor subtype in biochemical and molecular effects of leptin. The relaxant response to leptin was greater in mid-pregnancy compared to late pregnancy and was mediated by the activation of BKCa channels by eNOS-derived nitric oxide in an ObRb receptor-dependent manner. In comparison to mid-pregnancy, expression of short forms (mainly ObRa receptor) of the receptor was significantly increased in late pregnancy, whereas ObRb receptor expression was similar in both phases. The results of the study suggest that ObRb receptor mediates leptin-induced increase in eNOS expression and NO synthesis. Leptin-induced eNOS expression and activation cause cGMP-independent stimulation of BKCa channels causing uterine relaxation. Increased short forms of the receptors and reduced BKCa channels exert a negative effect on uterine relaxation in late pregnancy. Leptin may have a physiological role in maintaining uterine quiescence in mid-pregnancy and its reduced relaxant response in late gestation may facilitate labor. Further, ObRb receptor agonists may be useful in the management of preterm labor.
摘要：
这项研究的目的是确定妊娠中期和晚期小鼠子宫中瘦素松弛作用的受体亚型和潜在机制。我们确定了受体亚型的相对mRNA表达，eNOS,通过定量PCR和BKCa通道以及通过免疫组织化学的整体受体表达。进行了等距张力研究以评估瘦素的作用并描述其机制。ObRb受体的选择性siRNA用于确定受体亚型在瘦素的生化和分子效应中的参与。与妊娠晚期相比，妊娠中期对瘦素的松弛反应更大，并且是由eNOS衍生的一氧化氮以ObRb受体依赖性方式激活BKCa通道介导的。与怀孕中期相比，该受体的短形式（主要是ObRa受体）的表达在妊娠晚期显着增加，而ObRb受体在两个阶段的表达相似。研究结果表明，ObRb受体介导瘦素诱导的eNOS表达和NO合成增加。瘦素诱导的eNOS表达和活化引起cGMP非依赖性刺激BKCa通道,引起子宫松弛。增加的短形式的受体和减少的BKCa通道对妊娠晚期的子宫松弛产生负面影响。瘦素可能在维持妊娠中期子宫静止中起生理作用，其在妊娠后期减少的松弛反应可能有助于分娩。Further,ObRb受体激动剂可用于治疗早产。
