[OBSERVATIONS ON METHODS OF MEASUREMENT OF PLASMINOGEN. INFLUENCE OF PLASMIN INHIBITORS PRESENT IN EUGLOBULINS ON EVALUATION OF AMOUNT OF PLASMINOGEN IN THE SERUM AND PLASMA OF MAN].
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The studies showed that t-PA activity was elevated during the acute phase, remained elevated during the recovery stage and declined during the sequelar stage. Lowering of PAI activity was found during the acute phase, which was reversed during the recovery phase and remained significantly elevated during the sequelar stage compared with the controls (P less than 0.001), F test showed that both t-PA and PAI activities changed significantly during various stages (t-PA, P less than 0.01; PAI, P less than 0.001). Because of these changes, the ratio of PAI and t-PA fluctuated during different stages of the disease. This ratio decreased during the acute stage and came close to the normal levels during the recovery phase. The ratio, however, elevated abnormally during the sequelar stage, compared with healthy controls (P less than 0.05), In addition, the result of correlation test and linear regression analysis of serum t-PA and PAI activities in 54 cases showed a significant negative correlation (P less than 0.001) existed between t-PA and PAI activities. The balance of plasma t-PA and PAI activities have the function in maintaining the normal bloodstream in human body. In the process of disease, the abnormality of plasma t-PA and PAI activities may be the different pathological characteristics involved in this stagnation process. If coordinated with differentiation of syndrome in TCM, it may have the important significance to follow-up, and determine prognosis and early diagnosis for certain potential clinical stagnation of blood.
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In this study we have demonstrated that both granulosa and theca-interstitial cells of hypophysectomized rat ovaries are capable of synthesizing tPA and PAI-1. Injection of a GnRH agonist can markedly induce these gene expressions in the ovary in a cell-specific and time-coordinated manner, so that a surge of tPA mRNA and its activity in both granulosa and theca-interstitial cells was obtained just prior to ovulation. Theca-interstitial cells make PAI-1 become the most active in the ovary. Both the amount PAI-1 mRNA and its activity in the cells reach the maximum level 6 h before the tPA peak. By contrast, granulosa cells produce only a little amount of PAI-1 (most increase tPA activity), and both PAI-1 mRNA and activity in the cells reach the maximum after ovulation. The coordinated regulation of tPA and PAI-1 in the ovary may fine-tune the peak of tPA activity which may be important for the regulation of the ovulatory process. The changes of tPA and PAI-1 in the ovarian cells of hypophysectomized rats during GnRHa-induced ovulation are similar to that in intact rats during hCG-induced ovulation, suggesting that the ovulatory process can be modulated by different regulatory signals mediated by influencing the coordinated expression of both tPA and PAI-1.
In the present study, gonadotropin and gonadotropin-releasing hormone (GnRH) regulation of tPA and PAI-1 expression in PMSG-primed granulosa cells has been investigated. (i) Addition of gonadotropins (FSH and LH) and GnRH agonist (GnRHa) or PMA to the culture increases tPA activity; FSH (or LH) plus GnRHa (or PMA) in the culture further enhances the enzyme production to such an extent that a more obvious effect than the additive effect caused by these hormones used alone has been observed; (ii) in contrast, FSH and LH decrease PAI-1 activity, whereas GnRHa and PMA alone markedly increase PAI-1 mRNA level and PAI-1 activity. Because FSH and LH stimulate tPA production and have no significant effect on PAI-1 mRNA induction, the observed inhibition of PAI-1 activity by gonadotropins may be due to the occurrence of neutralization of PA and PAI-1 proteins in the conditioned media by the formation of complexes between PA and PAI-1; (iii) increases in PAI-1 mRNA level and activity by GnRH and PMA are completely inhibited by the co-addition of FSH or LH to the culture. It is, therefore, suggested that the mechanism of gonadotropin and GnRHa regulation of tPA and PAI-1 expression in granulosa cells is different.
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