Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases
Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases
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DOI：
10.1073/pnas.080073497
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发表时间：
2000-04-25
影响因子：
11.1
通讯作者：
Richards, JS
中科院分区：
文献类型：
--
作者：
Robker, RL;Russell, DL;Richards, JS
排卵是一个精确定时的过程，成熟的卵母细胞从卵泡中释放出来，这个过程是由垂体促黄体生成素（LH）激增启动的。暂时与许多基因的转录调节相关，并且推测涉及降解毛囊壁的特定蛋白酶的合成和/或激活。黄体酮受体 (PR) 是一种核受体转录因子，在排卵前卵泡的颗粒细胞中响应 LH 激增而被诱导，并且已被证明对于排卵至关重要，因为缺乏 PR 的小鼠无法排卵并且不育。使用这些小鼠作为模型来阐明排卵过程中 PR 调节的基因，我们发现基质金属蛋白酶 MMP-2 和 MMP-9 不是 PR 期间的靶标。相比之下，另外两种蛋白酶 ADAMTS-1（一种具有血小板反应蛋白样基序的解整合素和金属蛋白酶）和组织蛋白酶 L（一种溶酶体半胱氨酸蛋白酶）是 PR 作用的转录靶标。 ADAMTS-1 在排卵前卵泡的颗粒细胞中 LH 刺激后被诱导，并且取决于 PR。组织蛋白酶 L 是由卵泡刺激激素在生长卵泡的颗粒细胞中诱导产生的，但最高水平的组织蛋白酶 L mRNA 出现在排卵前卵泡中，以 PR 依赖性方式响应 LH。卵巢中两种受调节蛋白酶的鉴定，以及它们在无排卵 PR 敲除小鼠中的异常表达，表明每种蛋白酶在卵泡破裂中都发挥着关键作用，并且代表了我们对控制排卵的蛋白水解事件的理解的重大进展。
Ovulation is a precisely timed process by which a mature oocyte is released from an ovarian follicle, This process is initiated by the pituitary surge of luteinizing hormone (LH). is temporally associated with transcriptional regulation of numerous genes, and is presumed to involve the synthesis and/or activation of specific proteases that degrade the follicle wall. The progesterone receptor (PR), a nuclear receptor transcription factor, is induced in granulosa cells of preovulatory follicles in response to the LH surge and has been shown to be essential for ovulation, because mice lacking PR fail to ovulate and are infertile, Using these mice as a model in which to elucidate PR-regulated genes in the ovulation process, we show that the matrix metalloproteinases MMP-2 and MMP-9 are not targets of PR during ovulation, In contrast, two other proteases, ADAMTS-1 (A disintegrin and metalloproteinase with thrombospondin-like motifs) and cathepsin L (a lysosomal cysteine protease), are transcriptional targets of PR action. ADAMTS-1 is induced after LH stimulation in granulosa cells of preovulatory follicles and depends on PR. Cathepsin L is induced in granulosa cells of growing follicles by follicle-stimulating hormone, but the highest levels of cathepsin L mRNA occur in preovulatory follicles in response to LH in a PR-dependent manner. The identification of two regulated proteases in the ovary, together with their abnormal expression in anovulatory PR knockout mice, suggests that each plays a critical role in follicular rupture and represents a major advance in our understanding of the proteolytic events that control ovulation.