Hild-Petito S, Verhage H G, Fazleabas A T
Department of Obstetrics and Gynecology, University of Illinois, Chicago 60612.
Endocrinology. 1992 Apr;130(4):2343-53. doi: 10.1210/endo.130.4.1372241.
Although estrogen and progesterone are essential for the establishment of pregnancy in primates, localization of their specific receptors in uterine cell types during pregnancy has not been investigated. Therefore, uteri were obtained from baboons during the menstrual cycle, after steroid treatment, or during early pregnancy on days 18, 25 and 32 postovulation. Uterine and placental tissues were also collected from baboons during late pregnancy. Tissues were processed for indirect immunocytochemical localization with specific monoclonal antibodies against estrogen receptor (ER; H222) and progestin receptor (PR; JZB39). Identification of specific cell types was confirmed by iron-hematoxylin/van Gieson and Gimori's stains. Specific staining for steroid receptors was detected only in the nucleus. In the absence of ovarian steroid hormones (ovariectomized baboons), ER were present in glandular epithelium, stroma, and myometrial smooth muscle cells (SMC). In contrast, PR were absent from all uterine cell types. In the estrogen-dominated (follicular and estradiol treatment) uterus, ER and PR were detected in the nuclei of glandular and surface epithelium, stroma, and myometrial SMC. Elevated progesterone levels (luteal or after progesterone treatment) resulted in a loss of nuclear ER in stroma and epithelium, except in the deep glandular epithelium in the basalis. PR was maintained in the stroma throughout the endometrium, but was detected only in the epithelium of the deep glands. The myometrial SMC contained both ER and PR. In early pregnancy, ER was absent from the glands and stroma as early as day 18 postovulation, but was present in the wall of spiral arteries, blood vessels, and myometrial SMC. On day 18 postovulation, staining for PR was absent from all glandular epithelium, but was maintained in the stroma surrounding the glands and spiral arteries, the wall of spiral arteries, blood vessels, and myometrial SMC. Stroma away from glandular epithelium contained few PR-positive cells. This staining pattern persisted throughout early pregnancy. No apparent differences in ER and PR localization were evident between the implantation and nonimplantation sites of the endometrium and myometrium. In late pregnancy, ER were only present in the SMC of the myometrium; however, PR were detected in stroma and myometrial SMC. The maternally derived decidua expressed PR, but not ER, in the majority of cells. In contrast, fetally derived tissues, placenta, and amnio-chorion, did not contain either ER or PR at any stage of pregnancy. Clearly, ER and PR persist in particular uterine cell compartments despite the continual high levels of progesterone in pregnancy and, thus, support a receptor-mediated mechanism for estrogen and progesterone regulation of implantation and pregnancy.
尽管雌激素和孕酮对于灵长类动物建立妊娠至关重要,但它们的特异性受体在妊娠期间子宫细胞类型中的定位尚未得到研究。因此,在月经周期、类固醇治疗后或排卵后第18、25和32天的早孕期间从狒狒获取子宫。在妊娠晚期也从狒狒收集子宫和胎盘组织。用针对雌激素受体(ER;H222)和孕激素受体(PR;JZB39)的特异性单克隆抗体对组织进行间接免疫细胞化学定位处理。通过铁苏木精/范吉森染色和吉姆利氏染色确认特定细胞类型的鉴定。类固醇受体的特异性染色仅在细胞核中检测到。在缺乏卵巢类固醇激素(去卵巢狒狒)的情况下,ER存在于腺上皮、基质和子宫肌层平滑肌细胞(SMC)中。相比之下,所有子宫细胞类型中均不存在PR。在雌激素占主导的(卵泡期和雌二醇治疗)子宫中,在腺上皮和表面上皮、基质和子宫肌层SMC的细胞核中检测到ER和PR。孕酮水平升高(黄体期或孕酮治疗后)导致基质和上皮细胞核ER丧失,但基底深层腺上皮除外。PR在整个子宫内膜的基质中持续存在,但仅在深层腺体的上皮中检测到。子宫肌层SMC同时含有ER和PR。在早孕时,早在排卵后第18天,腺体和基质中就不存在ER,但存在于螺旋动脉壁、血管和子宫肌层SMC中。在排卵后第18天,所有腺上皮均未检测到PR染色,但在腺体和螺旋动脉周围的基质、螺旋动脉壁、血管和子宫肌层SMC中持续存在。远离腺上皮的基质中PR阳性细胞很少。这种染色模式在整个早孕期间持续存在。子宫内膜和子宫肌层的着床部位与非着床部位之间在ER和PR定位上没有明显差异。在妊娠晚期,ER仅存在于子宫肌层的SMC中;然而,在基质和子宫肌层SMC中检测到PR。母体来源的蜕膜在大多数细胞中表达PR,但不表达ER。相比之下,胎儿来源的组织、胎盘和羊膜 - 绒毛膜在妊娠的任何阶段都不含有ER或PR。显然,尽管妊娠期间孕酮持续处于高水平,但ER和PR在特定的子宫细胞区室中持续存在,因此支持雌激素和孕酮对着床和妊娠进行受体介导调节的机制。