Progesterone receptor isoforms A and B: Temporal and spatial differences in expression during murine mammary gland development
Progesterone receptor isoforms A and B: Temporal and spatial differences in expression during murine mammary gland development
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DOI：
10.1210/en.2005-0346
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发表时间：
2005-08-01
期刊：
影响因子：
4.8
通讯作者：
Haslam, SZ
中科院分区：
文献类型：
--
作者：
Aupperlee, MD;Smith, KT;Haslam, SZ
黄体酮是乳腺中有效的有丝分裂原。根据使用工程化表达孕激素受体 (PR) 亚型 A 或 B 的细胞和动物进行的研究，PRA 和 PRB 被认为具有不同的功能。使用仅针对 PRA 或仅针对 PRB 的特异性抗体的免疫组织化学方法，我们发现在 BALB/c 小鼠的正常乳腺发育过程中，乳腺上皮细胞中的 PRA 和 PRB 表达在时间和空间上是分离的。在处女乳腺中，当导管发育活跃时，唯一表达的 PR 蛋白亚型是 PRA。 PRA 水平在怀孕期间显着降低，表明在这一发育阶段的作用较小。 PRB 仅在怀孕期间、肺泡形成期间大量表达。 PRA 和 PRB 共定位仅发生在一小部分细胞中。妊娠期间，PRB 与 5-溴-2'-脱氧尿苷 (BrdU) 和细胞周期蛋白 D1 广泛共定位； 95% 的 BrdU 阳性细胞和 83% 的细胞周期蛋白 D1 阳性细胞表达 PRB。妊娠期间未观察到 PRA 与 BrdU 或细胞周期蛋白 D1 共定位。在处女腺中，PRA 与 BrdU 或细胞周期蛋白 D1 的共定位较低；仅 27% 的 BrdU 阳性细胞和 4% 的细胞周期蛋白 D1 阳性细胞表达 PRA。这些发现意味着，体内 PRB 阳性细胞与 PRA 阳性细胞中孕酮的作用不同。小鼠乳腺中 PR 亚型表达的空间和时间分离为确定 PRA 与 PRA 的特定功能提供了独特的机会。
Progesterone is a potent mitogen in the mammary gland. Based on studies using cells and animals engineered to express progesterone receptor (PR) isoforms A or B, PRA and PRB are believed to have different functions. Using an immunohistochemical approach with antibodies specific for PRA only or PRB only, we show that PRA and PRB expression in mammary epithelial cells is temporally and spatially separated during normal mammary gland development in the BALB/c mouse. In the virgin mammary gland when ductal development is active, the only PR protein isoform expressed was PRA. PRA levels were significantly lower during pregnancy, suggesting a minor role at this stage of development. PRB was abundantly expressed only during pregnancy, during alveologenesis. PRA and PRB colocalization occurred in only a small percentage of cells. During pregnancy there was extensive colocalization of PRB with 5-bromo-2'-deoxyuridine ( BrdU) and cyclin D1; 95% of BrdU-positive cells and 83% of cyclin D1-positive cells expressed PRB. No colocalization of PRA with either BrdU or cyclin D1 was observed at pregnancy. In the virgin gland, PRA colocalization with BrdU or cyclin D1 was low; only 27% of BrdU-positive cells and 4% of cyclin D1-positive cells expressed PRA. The implication of these findings is that different actions of progesterone are mediated in PRB positive vs. PRA-positive cells in vivo. The spatial and temporal separation of PR isoform expression in mouse mammary gland provides a unique opportunity to determine the specific functions of PRA vs.