Ovarian steroid hormones regulate granulocyte-macrophage colony-stimulating factor synthesis by uterine epithelial cells in the mouse
Ovarian steroid hormones regulate granulocyte-macrophage colony-stimulating factor synthesis by uterine epithelial cells in the mouse
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DOI：
10.1095/biolreprod54.1.183
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发表时间：
1996-01-01
影响因子：
3.6
通讯作者：
Seamark, RF
中科院分区：
文献类型：
--
作者：
Robertson, SA;Mayrhofer, G;Seamark, RF
体外研究表明，子宫上皮细胞是炎性细胞因子粒细胞-巨噬细胞集落刺激因子(GM-CSF)的有效来源，原位杂交证实在完整的子宫内膜中腔上皮和腺上皮是GM-CSF表达的主要部位。为了研究卵巢类固醇激素在GM-CSF合成中的作用，对卵巢切除、类固醇替代或类固醇拮抗剂干扰激素水平的小鼠子宫内膜细胞的短期原代培养上清液中GMCSF生物活性进行了测定。在发情周期的不同时间收获的细胞中，GM-CSF的产生有波动，在发情期达到顶峰。去卵巢小鼠子宫内膜细胞产生的GM-CSF比发情小鼠的少25倍，如果去卵巢小鼠在收获前3小时或更长时间给予雌激素而不是孕酮，其产生的GM-CSF就会增加。雌激素诱导的这种增加可通过联合给药黄体酮或诱导蜕膜反应来抑制，并被雌激素拮抗剂ZK119,010阻断。相比之下，用抗孕激素RU486预处理的小鼠显著增加了雌激素和孕酮联合使用的去卵巢小鼠细胞中GM-CSF的产量，并拮抗了hCG处理的小鼠细胞中GM-CSF释放的抑制。这些研究表明，子宫上皮细胞合成和/或释放GM-CSF受到雌激素的刺激，而孕酮具有中等程度的抑制作用。用定量逆转录-聚合酶链式反应分析激素处理的去卵巢小鼠子宫上皮细胞培养和完整子宫中GM-CSF mRNA的表达，表明雌激素和孕酮对GM-CSF释放的影响至少部分是在转录水平上介导的。这些发现表明GM-CSF是激素驱动的子宫内膜周期和着床前重塑事件的局部介质，可能通过粒细胞和巨噬细胞的募集和行为调节发挥作用。
Uterine epithelial cells have been shown by in vitro studies to be a potent source of the inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), and the luminal and glandular epithelium has been confirmed as the predominant site of GM-CSF expression in the intact endometrium by in situ hybridization. To examine the role of ovarian steroid hormones in GM-CSF synthesis, GMCSF bioactivity has been measured in the supernatants of short-term primary cultures of endometrial cells prepared from mice in which steroid levels were perturbed by ovariectomy and steroid replacement or by steroid antagonists. GM-CSF production was found to fluctuate in cells harvested at different times during the estrous cycle, peaking at estrus. Endometrial cells derived from ovariectomized mice produced 25-fold less GM-CSF than did cells from estrous mice, and production was increased if ovariectomized mice were pretreated with estrogen, but not progesterone, 3 h or more before harvest. This estrogen-induced increase was inhibited by coadministration of progesterone or by induction of a decidual response and was blocked by the estrogen antagonist ZK 119,010. By contrast, pretreatment of mice with the anti-progestin RU486 significantly elevated GM-CSF output in cells from ovariectomized mice given estrogen and progesterone in combination and antagonized the inhibition of GM-CSF release seen in cells harvested from mice treated with hCG. These studies demonstrate that GM-CSF synthesis and/or release by uterine epithelial cells is stimulated by estrogen, with progesterone having a moderate inhibitory effect. Analysis of GM-CSF mRNA expression in uterine epithelial cell cultures and in intact uteri from steroid hormone-treated ovariectomized mice by quantitative reverse transcription-polymerase chain reaction indicated that the effects of estrogen and progesterone on GM-CSF release are mediated at least in part at the transcriptional level. These findings implicate GM-CSF as a local mediator of steroid-driven remodeling events in the cycling and preimplantation endometrium, possibly acting through the recruitment and behavioral regulation of granulocytes and macrophages.