Effects of ovarian hormone treatment on the gene expression of muscarinic acetylcholine receptors in the ovariectomized rat myometrium.
Effects of ovarian hormone treatment on the gene expression of muscarinic acetylcholine receptors in the ovariectomized rat myometrium.
复制标题
卵巢激素治疗对去势大鼠子宫肌层毒蕈碱乙酰胆碱受体基因表达的影响。
DOI：
10.1016/j.jsbmb.2014.02.012
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kanzaki H
中科院分区：
文献类型：
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作者：
Yasuda K;Sumi G;Kanamori C;Nakajima T;Tsuzuki T;Cho H;Nishigaki A;Okada H;Kanzaki H
本研究采用实时荧光定量PCR技术研究卵巢激素对子宫肌层毒毒碱乙酰胆碱受体（M1-M5）基因表达的影响，并评价其与卵巢激素受体（ERα、ERβ和PgR）基因表达的关系。Wistar大鼠假手术（SO）或去卵巢（OVX），从术后第33天开始，用载体、雌二醇（E2）、黄体酮（P4）或E2和P4同时治疗2天。肌层未检测到M1和M4 mRNA的表达。与SO组相比，OVX和OVX + P4组M2 mRNA表达无显著变化，但OVX + E2组M2 mRNA表达显著升高，OVX + E2P4组M2 mRNA表达趋于正常化。与SO组相比，OVX和OVX + P4组M3 mRNA表达显著升高，但OVX + E2和OVX + E2P4组M3 mRNA表达归一化。各实验组m5mrna表达无明显变化。与SO组相比，OVX、OVX + E2和OVX + P4组ERα mRNA表达显著升高，但OVX + E2P4组ERα mRNA表达趋于正常。各实验组ERβ mRNA表达变化与M3 mRNA表达变化相似。相比之下，各实验组PgR mRNA表达变化与M2、M3、M5 mRNA表达变化不一致。此外，我们还评估了毒蕈碱类乙酰胆碱受体与卵巢激素受体在发情周期中的表达关系。与发情前期和发情期相比，M2 mRNA在发情期和后发期的表达明显增加。M3 mRNA表达仅在疫期较其他时期显著升高。相比之下，m5mrna的表达在发情周期内没有变化。ERα mRNA在发情周期的表达变化与M2相似，但差异不显著。ERβ mRNA表达变化与M3 mRNA表达变化相似。PgR mRNA在发情期的表达变化明显高于发情期，但与M2、M3、M5 mRNA在发情期的表达变化不一致。对比发情期和发情期肌层对乙酰胆碱的敏感性，发情期的敏感性明显低于发情期。这些结果提示卵巢激素通过调节激素受体的表达影响子宫肌层M2和M3的表达。E2可通过ERα上调M2，而P4可通过PgR抑制ERα下调M2。E2可能通过抑制ERβ下调M3，而P4可能不调节M3和ERβ的表达。M5可能是肌层的组成型毒蕈碱受体，因为E2和P4都不影响M5的表达。E2和P4的结合可能通过抑制乙酰胆碱诱导的子宫肌收缩而促进生殖。
We investigate the effects of ovarian hormone on the gene expression of muscarinic acetylcholine receptors (M1–M5) in the myometrium using real-time PCR and evaluate the relationships between their expression and that of ovarian hormone receptors (ERα, ERβ, and PgR). Wistar rats were sham operated (SO) or ovariectomized (OVX) and treated with vehicle, estradiol (E2), progesterone (P4), or both E2 and P4 for 2 days beginning on postoperative day 33.M1 and M4 mRNA expressions were not detected in the myometrium. M2 mRNA expression did not change significantly in the OVX and OVX + P4 groups compared to the SO group, but increased significantly in the OVX + E2 group and was normalized in the OVX + E2P4 group. M3 mRNA expression increased significantly in the OVX and OVX + P4 groups compared to the SO group, but was normalized in the OVX + E2 and OVX + E2P4 groups. M5 mRNA expression did not change significantly in all experimental groups. ERα mRNA expression increased significantly in the OVX, OVX + E2, and OVX + P4 groups compared to the SO group, but was normalized in the OVX + E2P4 group. The changes in ERβ mRNA expression were similar to those of M3 mRNA expression in all experimental groups. In contrast, the changes in PgR mRNA expression did not correspond with that of M2, M3, or M5 mRNA expression in any of the experimental groups.Additionally, we evaluated the relationship between the expression of muscarinic acetylcholine receptors and ovarian hormone receptors in estrus cycle. M2 mRNA expression increased significantly in diestus and metaestrus compared in proestrus and estrus. M3 mRNA expression increased significantly in only diestrus compared in the other stages. In contrast, M5 mRNA expression did not change in estrus cycle. The changes in ERα mRNA expression appeared to be similar to those of M2 in estrus cycle, but no significant difference was found. The changes in ERβ mRNA expression were similar to those of M3 mRNA expression. The change in PgR mRNA expression increased significantly in diestrus compared in metaestrus, but did not correspond with that of M2, M3, or M5 mRNA expression in estrus cycle. When acetylcholine sensitivity in the myometrium was compared between diestrus and estrus, the sensitivity is significantly lower in estrus than in diestrus.These results suggest that ovarian hormones influence the expression of M2 and M3 in the myometrium by regulating the expression of hormone receptors. E2 may upregulate M2 via ERα, but P4 may downregulate M2 by inhibiting ERα via PgR. E2 may downregulate M3 by inhibiting ERβ, but P4 may not regulate the expression of M3 and ERβ. M5 may be a constitutive muscarinic receptor in the myometrium because neither E2 nor P4 influence the expression of M5. The combination of E2 and P4 may contribute the reproduction by quieting down the acetylcholine-induced myometrial contraction.