An autocrine progesterone positive feedback loop mediates oxytocin upregulation in bovine granulosa cells during luteinization.
An autocrine progesterone positive feedback loop mediates oxytocin upregulation in bovine granulosa cells during luteinization.
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DOI：
10.1210/en.138.11.5059
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发表时间：
1997-11-01
期刊：
影响因子：
4.8
通讯作者：
Ivell, R
中科院分区：
文献类型：
--
作者：
Lioutas, C;Einspanier, A;Ivell, R
体外培养的牛颗粒细胞在胰岛素或胰岛素加Forsklin的作用下黄体生成过程中，不仅孕酮的产生大量上调，而且缩氨酸激素催产素的基因也大量上调，并将多肽分泌到培养液中。通过使用孕激素受体拮抗剂RU486或奥那普司酮，我们已经证明催产素基因的这种上调是由一个涉及内源性孕酮和颗粒细胞中孕酮受体的自分泌环介导的。抗孕激素对催产素基因表达的抑制作用可被醋酸甲羟孕酮逆转，但不能被地塞米松逆转，表明这种作用是由内源性孕酮引起的。由于催产素似乎也参与了调节类固醇输出的正反馈回路，这些结果表明内源性孕酮本身是一系列被称为黄体素化的事件的关键反馈元素，并且可能的抗孕激素可以通过直接扰乱这一过程来影响体内的卵巢功能。
During luteinization of bovine granulosa cells in vitro in the presence of insulin, or insulin plus forskolin, there is a massive upregulation not only of progesterone production, but also of the gene for the peptide hormone oxytocin, with secretion of the peptide into the medium. By using the progesterone receptor antagonists, RU486 or onapristone, we have shown that this upregulation of the oxytocin gene is mediated by an autocrine loop involving endogenous progesterone and the progesterone receptor in the granulosa cells. The inhibition of oxytocin gene expression by the anti-gestagens can be reversed by medroxyprogesterone acetate but not by dexamethasone, showing that the effect is due to the endogenous progesterone. Since oxytocin also appears to be involved in a positive feedback loop regulating steroid output, these results show that endogenous progesterone itself is a key feedback element in the cascade of events termed luteinization, and that possibly anti-gestagens can influence ovarian function in vivo by directly disrupting this process.