Estradiol/Progesterone Interaction in Normal and Pathologic Breast Cells
Estradiol/Progesterone Interaction in Normal and Pathologic Breast Cells
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正常和病理性乳腺细胞中雌二醇/孕酮的相互作用
DOI：
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发表时间：
1986
影响因子：
5.2
通讯作者：
A. Gompel
中科院分区：
文献类型：
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作者：
P. Mauvais‐Jarvis;F. Kuttenn;A. Gompel
在女性生殖道的大多数靶细胞中，通过雌二醇（E2）和孕酮（P）的连续和协同作用获得足够的细胞分化。这主要是由于孕酮受体（PR）的合成涉及雌二醇通过其受体（ER）的优先作用。在正常乳腺中，E2刺激导管系统的生长，而小叶的发育取决于孕酮的分泌。换句话说，当E2 + P以适当的平衡分泌时，允许乳腺的完全和适当的发育。另一方面，孕酮也可能对E2有拮抗作用。孕酮的抗雌激素活性是通过减少E2受体的补充和17 β-羟基类固醇脱氢酶的合成介导的，这导致E2在靶器官本身中加速代谢为E1。这些在子宫内膜中已被充分证实的生化事件，也在正常乳腺上皮细胞培养物以及高细胞密度的分化纤维腺瘤中显示。此外，来自文献的数据表明，添加到人类乳腺细胞中的E2最终通过合成生长因子来增加细胞增殖。孕酮和孕激素具有相反的作用。我们实验室的数据表明，在正常培养的细胞中，E2和孕激素也是细胞增殖的拮抗剂。从这些不同的数据，它是假定，在人类中，长期的黄体期缺陷，导致一个不受阻碍的雌激素效应可能是一个促进乳腺癌的发生。
In most target cells of the female genital tract, adequate cell differentiation is obtained via the successive and synergistic actions of estradiol (E2) and progesterone (P). This mainly due to the fact that progesterone receptor (PR) synthesis involves the prior action of estradiol through its receptor (ER). In normal breast, E2 stimulates the growth of the ductal system whereas lobular development depends on progesterone secretion. In other words E2 + P, when secreted in an adequate balance, permit the complete and proper development of the mammary gland. On the other hand progesterone may also have an antagonistic action against E2. The antiestrogen activity of progesterone is mediated through a decrease in the replenishment of E2 receptor and the synthesis of 17 beta-hydroxysteroid dehydrogenase, which leads to an accelerated metabolism of E2 to E1 in the target organ itself. These biochemical events, which have been well documented in the endometrium, have also been shown in cultures of normal breast epithelial cells as well as in differentiated fibroadenomas with high cellular density. In addition, data from the literature show that E2 added to human breast cells increases cell multiplication by means, eventually, of the synthesis of growth factors. Progesterone and progestins have a reverse effect. Data from our laboratory indicate that in normal cultured cells E2 and progestins are also antagonists with regard to cell multiplication. From these different data, it is postulated that in human beings, long periods of a luteal-phase defect leading to an unopposed estrogen effect might be a promoter of carcinogenesis in the breast.