Progesterone upregulates calcitonin gene-related peptide and adrenomedullin receptor components and cyclic adenosine 3'5'-monophosphate generation in Eker rat uterine smooth muscle cell line.
Progesterone upregulates calcitonin gene-related peptide and adrenomedullin receptor components and cyclic adenosine 3'5'-monophosphate generation in Eker rat uterine smooth muscle cell line.
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黄体酮上调 Eker 大鼠子宫平滑肌细胞系中降钙素基因相关肽和肾上腺髓质素受体成分以及环腺苷 35-单磷酸的生成。
DOI：
10.1095/biolreprod.104.033779
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Yallampalli,Chandrasekhar
中科院分区：
文献类型：
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作者：
Thota,Chandrasekhar;Yallampalli,Chandrasekhar
降钙素基因相关肽(CGRP)和肾上腺髓质素(AM)是两种有效的平滑肌松弛药，已被证明能引起子宫松弛。子宫中CGRP和AM的结合部位在妊娠期间增加，在分娩和产后减少。这些结合位点的变化似乎与降钙素受体样受体(CRLR)、受体活性修饰蛋白1(RAMP1)、RAMP2和RAMP3mRNA水平的变化有关。然而，目前尚不清楚这些受体成分的变化是否发生在子宫肌层细胞中，以及类固醇激素是否可以直接改变肌肉细胞中的这些受体成分。此外，降钙素基因相关肽和AM信号在大鼠子宫肌层中的作用机制尚不清楚。因此，我们在EKER大鼠子宫肌层细胞系中检测了cAMP和cGMPCGRP和AM受体组分、G蛋白GαS、CGRP和AM对cAMP和cGMPmRNA表达的影响，以及孕酮对这些参数的影响。ELT3细胞表达CGRP和AM受体成分CRLR、RAMP1、RAMP2和RAMP3。孕酮处理组CRLRRAMP1mRNA表达增加，雌二醇17β处理组CRLRRAMP1mRNA表达降低。但孕酮和雌二醇均不影响RAMP和RAMP3mRNA的表达。孕酮增加GαS的表达，并增强CGRP和AM诱导的cAMP水平的升高。在子宫平滑肌细胞中，G-α、S蛋白拮抗剂NF449可降低基础cAMP水平以及cAMP和cAMP刺激的cAMP水平。所有细胞处理都不影响循环GMP的产生。我们的结果提示，孕酮刺激的子宫肌层细胞CGRP和AM受体、GαS蛋白水平的升高以及cAMP的产生可能是孕期子宫对CGRP和AM的敏感性增加的原因。
Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM), two potent smooth-muscle relaxants, have been shown to cause uterine relaxation. Both CGRP- and AM-binding sites in the uterus increase during pregnancy and decrease at labor and postpartum. These changes in binding sites appear to be related to the changes in calcitonin receptor-like receptor (CRLR), receptor activity-modified protein 1 (RAMP1), RAMP2, and RAMP3mRNA levels. It is not clear, however, whether the changes in the receptor components occur in the myometrial cells and whether the steroid hormones can directly alter these receptor components in the muscle cells. In addition, the mechanism of CGRP and AM signaling in the rat myometrium is not well understood. Therefore, we examined the mRNA expression of CGRP- and AM-receptor components, G protein Gαs, CGRP, and AM stimulation of cAMP and cGMP, and the effects of progesterone on these parameters in the Eker rat uterine myometrial smooth-muscle cell line (ELT3). ELT3 cells expressed CGRP- and AM-receptor components CRLR, RAMP1, RAMP2, and RAMP3. Expression of CRLR and RAMP1mRNA increased with progesterone treatment and decreased with estradiol-17β treatment. However, RAMP2and RAMP3mRNA expressions were unaltered by both progesterone and estradiol. Progesterone increased (P< 0.05) Gαs expression and augmented CGRP- and AM-induced increases in cAMP levels. In uterine smooth-muscle cells, the antagonist to Gαs protein NF449 decreased basal as well as CGRP- and AM-stimulated cAMP levels. None of the cell treatments affected cyclic GMP production. Our results suggest that the progesterone-stimulated increases in CGRP and AM receptors, Gαs protein levels, and cAMP generation in the myometrial cells may be responsible for increased uterine relaxation sensitivity to CGRP and AM during pregnancy.