Epifano O, Riminucci M, Manna C, Apa R, Greco E, Lanzone A, Stefanini M, Canipari R
Istituto di Istologia ed Embriologia Generale, Università di Roma, La Sapienza, Italy.
J Clin Endocrinol Metab. 1994 Jan;78(1):174-9. doi: 10.1210/jcem.78.1.8288701.
Plasminogen activator (PA) production by granulosa cells has been demonstrated in several species. In the human ovary, tissue-type PA and urokinase-type PA antigens have been found in the follicular fluids, but neither PA activity nor mRNA for both enzymes was found in granulosa cells of preovulatory follicles. All of these studies were performed on granulosa cells collected from follicles immediately before ovulation, when the cells were already in the luteal phase. In the attempt to better characterize the PA/plasminogen system in the human ovary, we examined PA and PA inhibitor (PAI) production in cultures of granulosa cells obtained from normally cycling untreated women at different stages of the cycle. In addition, we analyzed granulosa-luteal cells obtained from hormonally stimulated women undergoing gamete intrafallopian tube transfer, as a model of late phase follicular development. Zymographic analysis as well as immunoprecipitation with specific antisera revealed that granulosa cells from follicles at early phases of antral stages secreted high levels of PA of the urokinase type in the medium. No free tissue-type PA activity was found in any of the examined samples. On the contrary, free PAI was undetectable in medium obtained from granulosa cell cultures, and it was abundant in granulosa-luteal cell cultures, where it was found in two forms. These data show that in the human ovary as in that of the rat, PAs and PAIs are tightly time regulated. The timing of PA production in human granulosa cells suggests a role for PA activity at early stages of follicular maturation.
在多个物种中已证实颗粒细胞可产生纤溶酶原激活物（PA）。在人类卵巢中，已在卵泡液中发现组织型PA和尿激酶型PA抗原，但在排卵前卵泡的颗粒细胞中未发现这两种酶的PA活性及mRNA。所有这些研究都是在排卵前即刻从卵泡收集的颗粒细胞上进行的，此时细胞已处于黄体期。为了更好地描述人类卵巢中的PA/纤溶酶原系统，我们检测了从处于月经周期不同阶段的正常月经周期未治疗女性获取的颗粒细胞培养物中PA和PA抑制剂（PAI）的产生情况。此外，我们分析了从接受配子输卵管内移植的激素刺激女性获取的颗粒黄体细胞，作为卵泡晚期发育的模型。酶谱分析以及用特异性抗血清进行免疫沉淀显示，窦前阶段早期卵泡的颗粒细胞在培养基中分泌高水平的尿激酶型PA。在所检测的任何样本中均未发现游离的组织型PA活性。相反，在从颗粒细胞培养物获得的培养基中未检测到游离PAI，而在颗粒黄体细胞培养物中PAI丰富，且发现有两种形式。这些数据表明，在人类卵巢中与在大鼠卵巢中一样，PA和PAI受到严格的时间调控。人类颗粒细胞中PA产生的时间表明PA活性在卵泡成熟早期发挥作用。
