Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA.
Biol Reprod. 2010 Jul;83(1):147-54. doi: 10.1095/biolreprod.109.079947. Epub 2010 Apr 7.
The process of ovulation involves weakening of the follicular wall by proteolytic enzymes. The function of FURIN (also known as PCSK3) is to activate various proteolytic enzymes. In the present study, the expression, localization, and function of FURIN were investigated in the periovulatory rat ovary. Immature female rats were injected with equine chorionic gonadotropin followed by human chorionic gonadotropin (hCG) 48 h later to stimulate ovulation. Ovaries were collected at 0, 4, 8, 12, and 24 h after hCG injection. Administration of hCG increased Furin mRNA expression in both intact ovaries and cultured ovarian follicles to maximal levels at 8 and 12 h before decreasing at 24 h. In cultured granulosa cells, Furin mRNA levels were significantly induced at 12 h after hCG. In situ hybridization of Furin mRNA demonstrated expression in the granulosa cells, with predominant expression in the theca layer. Regulation studies demonstrated that Furin mRNA was induced in residual tissue by forskolin or amphiregulin. To examine the role of FURIN in protease activation and ovulation, rats were treated with a FURIN inhibitor and oocyte release was determined. There was a 38% decrease in the number of oocytes released in ovaries treated with the FURIN inhibitor. Likewise, the FURIN inhibitor decreased the activation of MMP2. The induction of Furin mRNA after treatment with hCG, along with the decrease in MMP2 activation and oocyte release after FURIN inhibition, supports the hypothesis that FURIN is upregulated during the preovulatory period, which results in activation of proteinases associated with the breakdown of the follicular wall during ovulation.
排卵过程涉及蛋白水解酶对卵泡壁的削弱。丝氨酸蛋白酶原 2 转化酶（FURIN）（也称为 PCSK3）的功能是激活各种蛋白水解酶。在本研究中，研究了 FURIN 在发情期大鼠卵巢中的表达、定位和功能。将未成熟雌性大鼠注射马绒毛膜促性腺激素，然后在 48 小时后注射人绒毛膜促性腺激素（hCG）以刺激排卵。在 hCG 注射后 0、4、8、12 和 24 小时收集卵巢。hCG 给药增加了完整卵巢和培养的卵巢卵泡中 Furin mRNA 的表达，在 hCG 注射后 8 和 12 小时达到最大水平，然后在 24 小时时降低。在培养的颗粒细胞中，hCG 后 12 小时 Furin mRNA 水平显着升高。原位杂交显示 Furin mRNA 在颗粒细胞中表达，在膜层中表达为主。调控研究表明，Furin mRNA 被 forskolin 或 Amphiregulin 诱导在残留组织中表达。为了研究 FURIN 在蛋白酶激活和排卵中的作用，用 FURIN 抑制剂处理大鼠，并确定卵母细胞的释放。用 FURIN 抑制剂处理的卵巢中释放的卵母细胞数量减少了 38％。同样，FURIN 抑制剂降低了 MMP2 的激活。用 hCG 处理后 Furin mRNA 的诱导，以及 FURIN 抑制后 MMP2 激活和卵母细胞释放的减少，支持了这样的假说，即在发情期前 FURIN 上调，导致与卵泡壁破裂相关的蛋白酶的激活排卵期间。
