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c-myc蛋白在小鼠子宫中的细胞类型特异性定位:类固醇激素的调节及着床前期分析

Cell type-specific localization of c-myc protein in the mouse uterus: modulation by steroid hormones and analysis of the periimplantation period.

作者信息

Huet-Hudson Y M, Andrews G K, Dey S K

机构信息

Department of Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City 66103.

出版信息

Endocrinology. 1989 Sep;125(3):1683-90. doi: 10.1210/endo-125-3-1683.

DOI:10.1210/endo-125-3-1683
PMID:2667965
Abstract

Estrogen has been shown to induce a rapid transient increase in c-myc mRNA in the rat uterus. However, no studies of the cell specificity of c-myc expression in the uterus have been reported, and nothing is known about the expression of c-myc in response to other steroids or during normal uterine preparation for implantation. To this end, the cell type-specific localization of c-myc protein was determined in the ovariectomized mouse uterus after progesterone (P4) and/or 17 beta-estradiol (E2) injection as well as during the periimplantation period. After E2 injection, a rapid accumulation of c-myc protein was detected exclusively in the uterine luminal and glandular epithelial nuclei in the ovariectomized mouse. Essentially all of these cells contained immunoreactive c-myc by 12 h postinjection. In contrast, after P4 injection, rapid accumulation of c-myc was noted exclusively in some of the stromal cell nuclei. Pretreatment of the ovariectomized mouse for 4 days with P4 (P4 priming) followed by E2 injection resulted in an increase in the number of c-myc-positive stromal cells, but few, if any, c-myc-positive cells were detected in the luminal and glandular epithelia. These uterine cell type-specific localizations of c-myc protein, induced by E2 or P4 injection, were followed within 18-24 h by DNA synthesis ([ 3H]thymidine incorporation) restricted to the epithelia or stroma, respectively. c-Myc was detected in the nuclei of luminal and glandular epithelia during proestrus and on days 1 and 2 of pregnancy, a period when the uterus is under the influence of estrogen. c-Myc-positive cells were detected in the stroma on day 3, and by day 4 a large number of stromal cell nuclei were c-myc positive. These changes are coincident with increasing P4 levels during early pregnancy. At the implantation chamber on day 5, many cells in the primary decidual zone as well as some of the deeper stromal cells were c-myc protein positive, whereas on day 6, c-myc protein was detected only in the secondary decidual zone. During this period of uterine preparation for embryo implantation and subsequent decidualization, there was a positive correlation between c-myc protein localized in specific populations of uterine cells and subsequent DNA synthesis in those cell types. Thus, both E2 and P4 induce cell type-specific accumulation of c-myc protein in the uterus of the ovariectomized mouse, with E2 induction of c-myc being restricted to epithelia, and P4 induction restricted to stroma.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

雌激素已被证明可诱导大鼠子宫中c-myc mRNA迅速短暂增加。然而,尚未有关于子宫中c-myc表达细胞特异性的研究报道,对于c-myc在其他类固醇作用下或在子宫为着床进行正常准备过程中的表达情况也一无所知。为此,我们确定了在切除卵巢的小鼠子宫中,注射孕酮(P4)和/或17β-雌二醇(E2)后以及在着床前期c-myc蛋白的细胞类型特异性定位。注射E2后,在切除卵巢的小鼠子宫腔和腺上皮细胞核中仅检测到c-myc蛋白迅速积累。注射后12小时,基本上所有这些细胞都含有免疫反应性c-myc。相反,注射P4后,仅在一些基质细胞核中注意到c-myc迅速积累。对切除卵巢的小鼠用P4预处理4天(P4预处理)后再注射E2,导致c-myc阳性基质细胞数量增加,但在腔上皮和腺上皮中几乎未检测到c-myc阳性细胞。由E2或P4注射诱导的子宫细胞类型特异性c-myc蛋白定位,在18 - 24小时内分别伴随着仅限于上皮或基质的DNA合成([3H]胸苷掺入)。在动情前期以及妊娠第1天和第2天,在子宫腔和腺上皮细胞核中检测到c-myc,此时子宫受雌激素影响。在第3天在基质中检测到c-myc阳性细胞,到第4天大量基质细胞核c-myc呈阳性。这些变化与妊娠早期P4水平升高一致。在第5天的着床腔,初级蜕膜区的许多细胞以及一些较深的基质细胞c-myc蛋白呈阳性,而在第6天,仅在次级蜕膜区检测到c-myc蛋白。在子宫为胚胎着床及随后蜕膜化做准备的这段时间里,子宫特定细胞群体中定位的c-myc蛋白与这些细胞类型随后的DNA合成之间存在正相关。因此,E2和P4均可诱导切除卵巢小鼠子宫中c-myc蛋白的细胞类型特异性积累,E2诱导的c-myc仅限于上皮,P4诱导的c-myc仅限于基质。(摘要截短至400字)

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