Axiotis C A, Guarch R, Merino M J, Laporte N, Neumann R D
Warren Grant Magnuson Clinical Center, Department of Nuclear Medicine, National Cancer Institute, Bethesda, Maryland.
Lab Invest. 1991 Nov;65(5):577-81.
To determine the expression, distribution, and intracellular localization of the multi-drug resistance gene product P-glycoprotein (Pgp) in the human menstrual cycle and in early gestational endometrium, we retrospectively studied 36 endometrial samples utilizing 3 murine monoclonal antibodies (MAbs), MAb C219, MAb C494, and MAb JSB-1, which recognize spatially distinct cytoplasmic epitopes of Pgp. Formalin-fixed, paraffin-embedded endometrial samples obtained from 36 women of reproductive age with normal menstrual cycles were assigned morphologic menstrual dates: proliferative (N = 10), secretory (N = 19), menstrual (N = 1), and gestational endometrium (N = 6). The cellular localization, staining intensity, and percentage of Pgp immunoreactive cells varied with the phase of the menstrual cycle. Early proliferative endometria revealed no Pgp immunoreactivity for all three MAbs. Mid-proliferative endometria showed weak immunostaining in less than 15% of the glandular epithelia. Late proliferative endometria showed a strong apical paranuclear/Golgi staining pattern. Early secretory endometria showed strong luminal membranous, subnuclear vacuolar membranous, and supranuclear vacuolar membranous immunostaining to all 3 MAbs in greater than 80% of the glandular epithelia. Apical paranuclear/Golgi and membranous staining were present in nonvacuolated mid-secretory glands. Immunoreactivity diminished in the late secretory phase with mild to moderate staining in less than 35% of the endometrial glands. Menstrual endometria showed weak, focal staining. All gestational endometria showed marked cytoplasmic, membranous, and apical/Golgi immunostaining both in the hypersecretory (Arias-Stella) endometrial glands as well as in the decidua. In general, the intensity of MAb C494 immunostaining was weaker than that of MAb C219 or JSB-1. These results suggest the following: Pgp expression parallels that of nuclear progesterone receptor expression in the normal human endometrial cycle and early gestational endometrium; Pgp expression corresponds to rising plasma and tissue levels of progesterone as well as to morphologic changes in the endometrial glandular epithelium associated with the marked development of the secretory apparatus; Pgp expression is hormonally regulated and may be involved in uteroplacental transport of substrates important in the implantation process and in early embryo-endometrial interactions; and Pgp may be involved in the transport of progesterone across the uterine epithelium during pregnancy.
为了确定多药耐药基因产物P-糖蛋白（Pgp）在人类月经周期及妊娠早期子宫内膜中的表达、分布和细胞内定位，我们利用3种鼠单克隆抗体（MAb），即识别Pgp不同空间细胞质表位的MAb C219、MAb C494和MAb JSB-1，对36份子宫内膜样本进行了回顾性研究。从36名月经周期正常的育龄妇女获取福尔马林固定、石蜡包埋的子宫内膜样本，并确定其形态学月经日期：增殖期（N = 10）、分泌期（N = 19）、月经期（N = 1）和妊娠子宫内膜（N = 6）。Pgp免疫反应性细胞的细胞定位、染色强度和百分比随月经周期阶段而变化。所有三种单克隆抗体对早期增殖期子宫内膜均未显示Pgp免疫反应性。增殖中期子宫内膜在不到15%的腺上皮中显示弱阳性染色。增殖晚期子宫内膜显示强烈的核旁/高尔基体顶端染色模式。早期分泌期子宫内膜在超过80%的腺上皮中对所有3种单克隆抗体均显示强烈的腔面膜、核下空泡膜和核上空泡膜免疫染色。核旁/高尔基体顶端和膜染色出现在非空泡化的分泌中期腺体中。分泌晚期免疫反应性减弱，不到35%的子宫内膜腺体有轻度至中度染色。月经期子宫内膜显示弱阳性、局灶性染色。所有妊娠子宫内膜在高分泌期（阿里亚斯-斯特拉）子宫内膜腺体以及蜕膜中均显示明显的细胞质、膜和顶端/高尔基体免疫染色。总体而言，MAb C494免疫染色强度弱于MAb C219或JSB-1。这些结果表明：在正常人类子宫内膜周期和妊娠早期子宫内膜中，Pgp表达与核孕酮受体表达平行；Pgp表达与血浆和组织中孕酮水平升高以及子宫内膜腺上皮形态学变化相对应，这些变化与分泌装置的显著发育有关；Pgp表达受激素调节，可能参与对植入过程和早期胚胎-子宫内膜相互作用重要的底物的子宫胎盘转运；并且Pgp可能参与妊娠期孕酮跨子宫上皮的转运。
