Mote Patricia A, Arnett-Mansfield Rebecca L, Gava Natalie, deFazio Anna, Mulac-Jericevic Biserka, Conneely Orla M, Clarke Christine L
Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, and Department of Gynecological Oncology, Westmead Hospital, New South Wales 2145, Australia.
Endocrinology. 2006 Dec;147(12):5503-12. doi: 10.1210/en.2006-0040. Epub 2006 Sep 15.
In rodents, progesterone receptors (PRs) A and B have different and often nonoverlapping roles, and this study asked whether different activities of the PR proteins in mouse are related to differences in their expression in reproductive tissues. The individual expression of PRA and PRB was determined immunohistochemically in mammary gland and uterus during the estrous cycle or in response to endocrine manipulation. In the mammary gland, PRA and PRB were colocated in PR+ epithelial cells, with little change during the estrous cycle. In the uterus, PRA was not detected in luminal epithelium at any stage of the cycle, and PR+ luminal cells expressed only PRB. In the stroma and myometrium, PRA and PRB levels fluctuated with cyclical systemic hormone exposure. Observation of functional end points suggested that augmented stromal and/or myometrial PRA in proestrus inhibited estrogen receptor expression and epithelial proliferation. Colocation of PRA and PRB was hormonally regulated, and ovariectomy did not reproduce the expression of PRA and PRB in the uterus during the estrous cycle. Whereas PRB was the only PR in the luminal epithelium in cycling mice, ovariectomy restored PRA expression, resulting in PRA-PRB colocation. In stroma and myometrium, PRA and PRB colocated in PR+ cells, but ovariectomy reduced PRA levels more than PRB, resulting in PRB-only-expressing cells. This study has shown that nonoverlapping PRA and PRB expression in the uterus, in particular the lack of PRA, and expression of PRB only in the luminal epithelium throughout the estrous cycle, is likely to contribute to the distinct roles of PRA and PRB in the adult mouse.
在啮齿动物中，孕激素受体（PRs）A和B具有不同且通常不重叠的作用，本研究探讨了小鼠中PR蛋白的不同活性是否与其在生殖组织中的表达差异有关。通过免疫组织化学方法测定动情周期或内分泌调控时乳腺和子宫中PRA和PRB的个体表达。在乳腺中，PRA和PRB共定位于PR+上皮细胞中，在动情周期中变化不大。在子宫中，在周期的任何阶段，腔上皮中均未检测到PRA，PR+腔细胞仅表达PRB。在基质和肌层中，PRA和PRB水平随周期性全身激素暴露而波动。功能终点观察表明，动情前期基质和/或肌层中PRA增加会抑制雌激素受体表达和上皮增殖。PRA和PRB的共定位受激素调节，卵巢切除术不能重现动情周期中子宫内PRA和PRB的表达。虽然PRB是动情周期小鼠腔上皮中的唯一PR，但卵巢切除术恢复了PRA表达，导致PRA-PRB共定位。在基质和肌层中，PRA和PRB共定位于PR+细胞中，但卵巢切除术使PRA水平比PRB降低得更多，导致仅表达PRB的细胞。本研究表明，子宫中PRA和PRB的不重叠表达，特别是PRA的缺乏，以及在整个动情周期中PRB仅在腔上皮中的表达，可能导致PRA和PRB在成年小鼠中发挥不同的作用。
