UTERINE ESTROGEN-RECEPTORS ARE INCREASED BY RU486 IN LATE PREGNANT RHESUS MACAQUES BUT NOT AFTER SPONTANEOUS LABOR
UTERINE ESTROGEN-RECEPTORS ARE INCREASED BY RU486 IN LATE PREGNANT RHESUS MACAQUES BUT NOT AFTER SPONTANEOUS LABOR
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DOI：
10.1210/jcem-70-1-181
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发表时间：
1990-01-01
影响因子：
5.8
通讯作者：
BRENNER, RM
中科院分区：
文献类型：
--
作者：
HALUSKA, GJ;WEST, NB;BRENNER, RM
黄体酮退出作为灵长类动物分娩的机制是有争议的。孕激素拮抗剂RU486，在妊娠后期给恒河猴以47 mmol/kg的剂量。日（20mg /kg .cntdot）天)，引起子宫活动增加，但不是预期的羊水前列腺素增加或宫颈扩张。因此，我们研究了RU486对妊娠后期和足月自然分娩后恒河猴生殖道组织雌激素受体（ER）定位和浓度的影响。采用免疫细胞化学技术和生物化学方法测定妊娠子宫组织中ER的分布，两种方法均采用ER特异性单克隆抗体。免疫细胞化学检查羊膜、绒毛膜未见ER；然而，与妊娠对照组织和分娩组织相比，RU486治疗后蜕膜和子宫肌层的受体染色明显增加。核(n)和细胞质(c) ER的蔗糖梯度测定显示，孕妇和产妇蜕膜中的ER（以雌二醇结合的fmol /mg DNA表示）水平较低(孕妇：nER = 7.3。2.4, cER = 17.1 .+-。6.4;产妇，nER = 7.7 +-。3.1, cER = 16.4 .+-。子宫肌层（妊娠：nER = 21.7 .+-）。4.1, cER = 20.8 .+-。5.3;产妇：nER = 30.0 .+-。2.8, cER = 10.7。6.7)。相比之下，RU 486处理的动物组织在蜕膜中含有高水平的ER (nER = 52.3 .+-。16.8, cER = 240.5 .+-。145.3)和肌层(nER = 77.0 .+-。19.2;cER = 66.5 .+-31.6)。我们得出结论：1)RU 486处理后蜕膜和子宫肌层ER的增加是由于孕酮对ER的抑制作用减弱，并证明RU 486在妊娠后期诱导子宫肌收缩过程中对孕酮受体的拮抗作用；2)羊膜和绒毛膜中ER的缺失表明，正常观察到的产程中恒河猴胎膜前列腺素生成的增加不是由ER介导的；3)对照妊娠猴和自然分娩猴蜕膜和子宫肌层中ER浓度没有变化，这表明雌激素受体的增加（由此推断，受体介导的黄体酮抑制的退出）不是灵长类动物准备分娩时正常事件的一部分。
Progesterone withdrawal as a mechanism for parturition in primates is controversial. The progesterone antagonist RU486, given in late pregnancy to rhesus monkeys at a dose of 47 mmol/kg .cntdot. day (20 mg/kg .cntdot. day), causes an increase in uterine activity, but not the expected increase in amniotic fluid prostaglandins or cervical dilatation. We, therefore, studied the effect of RU486 on estrogen receptor (ER) localization and concentration in reproductive tract tissues in rhesus monkeys during late gestation and after spontaneous labor at term. Distribution of ER in pregnant uterine tissues was studied by immunocytochemical techniques and quantified by a biochemical assay, both of which employed a monoclonal antibody specific for ER. ER was not present in amnion and chorion by immunocytochemical investigation; however, a significant increase in receptor staining was seen in decidua and myometrium after RU486 treatment compared to that in both pregnant control tissues and parturient tissues. Sucrose gradient assay of nuclear (n) and cytosolic (c) ER revealed a low level of ER (expressed as fmol of estradiol bound/mg of DNA) in pregnant and parturient decidua (pregnant: nER = 7.3 .+-. 2.4, cER = 17.1 .+-. 6.4; parturient, nER = 7.7 .+-. 3.1, cER = 16.4 .+-. 8.8) and myometrium (pregnant: nER = 21.7 .+-. 4.1, cER = 20.8 .+-. 5.3; parturient: nER = 30.0 .+-. 2.8, cER = 10.7 .+-. 6.7). In contrast, tissues collected from RU 486-treated animals contained high levels of ER in decidua (nER = 52.3 .+-. 16.8, cER = 240.5 .+-. 145.3) and myometrium (nER = 77.0 .+-. 19.2; cER = 66.5 .+-. 31.6). We conclude that 1) the increase in ER in decidua and myometrium after RU 486 treatment is the result of a decrease in the inhibitory action of progesterone on ER and documents the progesterone receptor antagonism by RU 486 during induced myometrial contractility in late pregnant rhesus monkeys; 2) the absence of ER from amnion and chorion indicates that the normally observed increase in prostaglandin production by rhesus fetal membranes during labor is not mediated by ER; and 3) the absence of a change in the concentration of ER in decidua and myometrium from pregnant control monkeys and those in spontaneous labor indicates that an increase in ER (and, by inference, a withdrawal of receptor-mediated progesterone inhibition) is not part of the normal events in preparation for parturition in primates.