Paracrine regulation of epithelial progesterone receptor by estradiol in the mouse female reproductive tract
Paracrine regulation of epithelial progesterone receptor by estradiol in the mouse female reproductive tract
复制标题
DOI：
10.1095/biolreprod62.4.831
复制
发表时间：
2000-04-01
影响因子：
3.6
通讯作者：
Cunha, GR
中科院分区：
文献类型：
--
作者：
Kurita, T;Lee, K;Cunha, GR
本文研究了17β雌二醇(E-2)对小鼠子宫和阴道上皮细胞孕激素受体(PR)的调节作用。在去卵巢小鼠中，PR在阴道间质和上皮中低表达，但在子宫上皮中高表达。E-2诱导阴道上皮和间质PR表达，但下调子宫上皮PR表达。对雌激素受体α(ERα)基因敲除(ERKO)小鼠的分析表明，ERα是雌激素诱导的阴道上皮和间质中PR表达的必要条件，也是E2诱导子宫上皮中PR表达下调的必要条件，但不是组成性表达。研究了E-2对野生型和ERKO小鼠阴道和子宫组织中PR的调节作用。在重组的阴道组织中，E-2仅在野生型上皮和/或间质中诱导PR。因此，在阴道中，E-2通过组织内的ERα直接诱导PR。相反，E-2只下调野生型间质构建的子宫组织重组的上皮PR。因此，E-2下调子宫上皮PR需要间质，而不是上皮性ERα。在体外，分离的子宫上皮细胞在有或没有E-2的情况下都保持了高水平的PR，这与体内对子宫上皮PR的间接调节是一致的。因此，E-2通过间质ERα介导的旁分泌机制下调子宫上皮中PR的表达。
Regulation of progesterone receptor (PR) by estradiol-17 beta (E-2) in mouse uterine and vaginal epithelia was studied. In ovariectomized mice, PR expression was low in both vaginal stroma and epithelium, but high in uterine epithelium. E-2 induced PR in vaginal epithelium and stroma, but down-regulated PR in uterine epithelium. Analysis of estrogen receptor alpha (ER alpha) knockout (ERKO) mice showed that ER alpha is essential for E-2-induced PR expression in both vaginal epithelium and stroma, and for E-2-induced down-regulation, but not constitutive expression of PR in uterine epithelium. Regulation of PR by E-2 was studied in vaginal and uterine tissue recombinants made with epithelium and stroma from wild-type and ERKO mice. In the vaginal tissue recombinants, PR was induced by E-2 only in wild-type epithelium and/or stroma. Hence, in vagina, E-2 induces PR directly via ER alpha within the tissue. Conversely, E-2 down-regulated epithelial PR only in uterine tissue recombinants constructed with wildtype stroma. Therefore, down-regulation of uterine epithelial PR by E-2 requires stromal, but not epithelial, ER alpha. In vitro, isolated uterine epithelial cells retained a high PR level with or without E-2, which is consistent with an indirect regulation of uterine epithelial PR in vivo. Thus, E-2 down-regulates PR in uterine epithelium through paracrine mechanisms mediated by stromal ER alpha.