Changes in the expression of calcitonin receptor-like receptor, receptor activity-modifying protein (RAMP) 1, RAMP2, and RAMP3 in rat uterus during pregnancy, labor, and by steroid hormone treatments'
Changes in the expression of calcitonin receptor-like receptor, receptor activity-modifying protein (RAMP) 1, RAMP2, and RAMP3 in rat uterus during pregnancy, labor, and by steroid hormone treatments'
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DOI：
10.1095/biolreprod.103.015628
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发表时间：
2003-10-01
影响因子：
3.6
通讯作者：
Yallampalli, C
中科院分区：
文献类型：
--
作者：
Thota, C;Gangula, PRR;Yallampalli, C
降钙素基因相关肽（CGRP）及其相关肽肾上腺髓质素（AM）是多种组织中有效的平滑肌松弛剂。据报道，CGRP在妊娠期间维持子宫舒张中起重要作用。我们以前曾报道过CGRP诱导的子宫舒张是受妊娠调节的。降钙素受体样受体（CRLR）是一种七结构域跨膜蛋白，与受体活性修饰蛋白（RAMP）1（一种单结构域跨膜蛋白）结合，作为CGRP-A受体发挥功能，而CRLR和RAMP 2或RAMP 3构成AM的受体。在目前的调查中，我们研究了CRLR，RAMP 1，RAMP 2，RAMP 3在大鼠子宫（n = 8）的mRNA表达的逆转录分析和聚合酶链反应，以评估在表达的变化CGRP-A-和AM-受体成分在妊娠和分娩过程中，并在成年卵巢切除大鼠类固醇激素治疗。mRNA的变化相对于18 S mRNA在不同阶段大鼠子宫中的表达：未妊娠、妊娠第18天、足月自然分娩、产后第2天和用RU 486处理的妊娠大鼠。切除卵巢的大鼠每天两次皮下给药3天。还检测了雌二醇-17 β（2.5 μ g/注射）、孕酮（2 mg/注射）以及雌二醇-17 β和孕酮的组合（与上述相同的剂量）对各种受体组分的表达的影响。结果显示，妊娠大鼠CRLR、RAMP 1、RAMP 2和RAMP 3的mRNA表达均显著高于非妊娠大鼠（P <0.001、P <0.01、P < 0.05和P < 0.01）。除RAMP 3外，其余3个基因的表达在分娩过程中均显著降低（P < 0.05）。孕激素拮抗剂RU 486在妊娠期间显著降低CRLR的所有受体成分（P < 0.01，RAMP 1、RAMP 2和RAMP 3的P < 0.05）。在成年去卵巢大鼠中，孕酮可引起CRLR（P < 0.001）、RAMP 1（P < 0.05）和RAMP 2（P < 0.01）的显著增加。RAMP 3的水平不受孕酮处理的影响。雌二醇-17 β处理显著降低了所有四种受体组分（CRLR P < 0.01，RAMP 1、RAMP 2和RAMP 3 P < 0.05）。我们的研究结果表明，CGRP和AM可能在妊娠期间的子宫静止中发挥作用，它们的受体成分受类固醇激素的调节。
Calcitonin gene-related peptide (CGRP) and its related peptide, adrenomedullin (AM), are potent smooth muscle relaxants in a variety of tissues. The CGRP has been reported to play an important role in maintaining uterine relaxation during pregnancy. We have previously reported that CGRP-induced uterine relaxation was gestationally regulated. Calcitonin receptor-like receptor (CRLR), a seven-domain transmembrane protein functions as CGRP-A receptor, in association with receptor activity-modifying protein (RAMP) 1, a single-domain transmembrane protein, whereas CRLR and RAMP2 or RAMP3 constitute a receptor for AM. In the present investigation, we examined the mRNA expression of CRLR, RAMP1, RAMP2, and RAMP3 in rat uterus (n = 8) by reverse transcriptional analysis and polymerase chain reaction to assess the changes in the expression of CGRP-A- and AM-receptor components during pregnancy and labor and by steroid hormone treatments in adult ovariectomized rats. The changes in mRNA are expressed relative to the 18S mRNA in the uterus of rats at various stages: nonpregnant, pregnant on Day 18, spontaneous labor at term, Day 2 postpartum, and in pregnant rats on treatment with RU486. Ovariectomized rats treated for 3 days twice daily s.c. with estradiol-17beta (2.5 mug/injection), progesterone(2 mg/injection), and the combination of estradiol-17beta and progesterone (same doses as above) were also examined for the expression of various receptor components. Results showed that mRNA expression of the receptor components was significantly higher (P < 0.001 for CRLR, P < 0.01 for RAMP1, P < 0.05 for RAMP2, and P < 0.01 for RAMP3) in pregnant compared to nonpregnant rats. Except for RAMP3, expression of all the other three genes decreased significantly (P < 0.05) during labor. A progesterone antagonist, RU486 significantly decreased (P < 0.01 for CRLR, P < 0.05 for RAMP1, RAMP2, and RAMP3) all the receptor components during pregnancy. In adult ovariectomized rats, progesterone caused significant increases in CRLR (P < 0.001), RAMP1 (P < 0.05), and RAMP2 (P < 0.01). Levels of RAMP3 were unaffected by the progesterone treatment. Estradiol-17beta treatment decreased all of the four receptor components significantly (P < 0.01 for CRLR, P < 0.05 for RAMP1, RAMP2, and RAMP3). Our results demonstrate that both CGRP and AM may play a role in uterine quiescence during pregnancy and that their receptor components are regulated by the steroid hormones.