Estrogen and progesterone regulate expression of the endothelins in the rhesus macaque endometrium
Estrogen and progesterone regulate expression of the endothelins in the rhesus macaque endometrium
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DOI：
10.1093/humrep/der115
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发表时间：
2011-07-01
影响因子：
6.1
通讯作者：
Slayden, Ov D.
中科院分区：
文献类型：
--
作者：
Keator, Christopher S.;Mah, Kuni;Slayden, Ov D.
背景：内皮素（EDN）被认为可以调节月经期间的子宫内膜血流、基质愈合和增殖期的子宫内膜生长。我们的目标是评估雌激素和孕激素对恒河猴子宫内膜 EDN 旁分泌系统的影响。方法：在本研究中，使用了存档的样本。这些样本是从切除卵巢的恒河猴身上采集的，这些猕猴依次用雌二醇 (E(2)) 治疗，然后用 E(2) 加黄体酮治疗，以产生人工月经周期。通过实时 PCR、原位杂交和免疫细胞化学分析人工周期的月经期、增殖期和分泌期动物的子宫内膜，以检测 EDN 肽（EDN1、EDN2、EDN3）、EDN 受体（EDNRA、EDNRB）、EDN 转换酶 1 (ECE1) 和膜金属内肽酶 (MME)（一种降解子宫内膜的酶）的变化。结果：与分泌后期相比，人工月经周期结束时黄体酮停药引发下一个周期月经期间上功能区EDN1、EDNRB和ECE1增加(P < 0.05)。在增殖期单独使用E(2)治疗可增加(P < 0.05) EDNRA转录本，该转录本主要局限于基质细胞。人工分泌期的 E(2) 加孕酮抑制 (P < 0.05) 功能区基质和上皮中 EDN3 的表达，趋于减弱 (P = 0.08) 上皮 EDN(2) 水平，并显着上调 (P < 0.05) MME 的基质表达。结论：我们的结果表明雌激素和孕激素调节 EDN 家族在月经周期期间。 EDN 旁分泌系统在分泌中期的变化可能表明 EDN 在胚胎植入过程中的作用。
BACKGROUND: Endothelins (EDNs) are thought to modulate endometrial blood flow during menses, stromal healing and endometrial growth during the proliferative phase. Our goal was to assess the effects of estrogen and progesterone on the EDN paracrine system in the endometrium of rhesus macaques.METHODS: In this study, archived samples were used. These samples were collected from oophorectomized rhesus macaques that were treated sequentially with estradiol (E(2)) and then E(2) plus progesterone to create artificial menstrual cycles. Endometrium from animals in the menstrual, proliferative and secretory phases of the artificial cycle were analyzed by real-time PCR, in situ hybridization and immunocytochemistry to detect changes in EDN peptides (EDN1, EDN2, EDN3), EDN receptors (EDNRA, EDNRB), EDN-converting enzyme 1 (ECE1) and membrane metalloendopeptidase (MME)-an enzyme that degrades the EDNs.RESULTS: Compared with the late secretory phase, progesterone withdrawal at the end of the artificial menstrual cycle triggered an increase (P < 0.05) in EDN1, EDNRB and ECE1 in the upper functionalis zone during menses of the next cycle. Treatment with E(2) alone in the proliferative phase increased (P < 0.05) EDNRA transcript, which was confined predominantly to the stromal cells. E(2) plus progesterone in the artificial secretory phase suppressed (P < 0.05) the expression of EDN3 in the functionalis zone stroma and epithelia, tended (P = 0.08) to attenuate levels of epithelial EDN(2) and markedly up-regulated (P < 0.05) the stromal expression of MME.CONCLUSIONS: Our results indicate that estrogen and progesterone regulate the EDN family during the menstrual cycle. The changes in the EDN paracrine system during the mid-secretory phase may indicate a role for EDN during embryo implantation.