Ny T, Liu Y X, Ohlsson M, Jones P B, Hsueh A J
J Biol Chem. 1987 Aug 25;262(24):11790-3.
Gonadotropin-releasing hormone (GnRH) acts directly on the ovary to induce ovulation in hypophysectomized proestrous rats. Because plasminogen activators (PAs) are implicated in gonadotropin-induced ovulation, we have studied the effect of GnRH on ovarian PA synthesis. GnRH induced tissue-type PA (tPA) secretion by cultured rat granulosa cells, but inhibited the secretion of urokinase-type PA. These effects were blocked by co-treatment with a GnRH antagonist, suggesting that stereospecific GnRH receptors are involved. Follicle-stimulating hormone (FSH) also induced tPA in granulosa cells but with a different time course than GnRH; the combined effect of FSH and GnRH was additive. The GnRH effect was mimicked by the calcium- and phospholipid-dependent protein kinase C activator, phorbol myristate acetate. In isolated cumulus-oocyte complexes and cumulus cells, GnRH treatment also increased tPA activity. In contrast, treatment of denuded oocytes with GnRH did not increase enzyme activity. After GnRH stimulation of the cumulus-oocyte complexes, tPA content in the denuded oocyte was elevated, suggesting that the cumulus cells mediate the action of GnRH to increase the oocyte enzyme levels. Hybridization experiments using a labeled rat tPA-specific DNA probe showed that both FSH and GnRH increased the level of tPA mRNA in cultured granulosa cells; the stimulatory effect of GnRH was blocked by the GnRH antagonist. Our results indicate that GnRH treatment increases tPA secretion by cultured granulosa cells and cumulus-oocyte complexes. The stimulation of enzyme activity in the granulosa cells is accompanied by increases in tPA mRNA levels.
促性腺激素释放激素（GnRH）可直接作用于卵巢，诱导垂体切除的动情前期大鼠排卵。由于纤溶酶原激活剂（PAs）与促性腺激素诱导的排卵有关，我们研究了GnRH对卵巢PA合成的影响。GnRH可诱导培养的大鼠颗粒细胞分泌组织型PA（tPA），但抑制尿激酶型PA的分泌。与GnRH拮抗剂共同处理可阻断这些效应，提示涉及立体特异性GnRH受体。促卵泡激素（FSH）也可诱导颗粒细胞产生tPA，但时间进程与GnRH不同；FSH和GnRH的联合作用是相加的。GnRH的作用可被钙和磷脂依赖性蛋白激酶C激活剂佛波酯肉豆蔻酸酯模拟。在分离的卵丘-卵母细胞复合体和卵丘细胞中，GnRH处理也可增加tPA活性。相反，用GnRH处理裸卵不会增加酶活性。GnRH刺激卵丘-卵母细胞复合体后，裸卵中的tPA含量升高，提示卵丘细胞介导GnRH的作用以增加卵母细胞的酶水平。使用标记的大鼠tPA特异性DNA探针进行的杂交实验表明，FSH和GnRH均可增加培养的颗粒细胞中tPA mRNA的水平；GnRH拮抗剂可阻断GnRH的刺激作用。我们的结果表明，GnRH处理可增加培养的颗粒细胞和卵丘-卵母细胞复合体中tPA的分泌。颗粒细胞中酶活性的刺激伴随着tPA mRNA水平的增加。
