Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasminogen activator (PA) is secreted cyclically (in stages VII and VIII) by rat seminiferous tubules. To investigate whether this can be maintained and influenced in vitro, tubule segments from stages VI and VIII of the epithelial cycle were cultured for 3 days in chemically defined medium supplemented with testosterone, FSH, or a combination of testosterone, FSH, insulin and retinoic acid (4F). Morphological and flow cytometric analyses of stage VI tubules suggested a roughly normal differentiation to stage VIII. They developed an increased PA secretion on day 3 of culture. Stage VIII tubules, however, did not develop all the characteristics of stage XII. Step 8 spermatids did not elongate and step 19 spermatids failed to develop into spermatozoa. Secretion of PA on day 3 was not significantly different to that on day 1. The 4F combination very significantly stimulated PA secretion in both stages, but FSH alone was effective only in stage VIII. Most of the secreted PA had a molecular weight of 43,000 in both stages, suggesting that it is of urokinase type. The results suggest that stage VI is more able to differentiate in vitro for 3 days than stage VIII; the cyclic secretion pattern of PA was partially maintained in tubule segments from stage VI. Follicle-stimulating hormone had an effect on PA secretion only in stage VIII, whereas the 4F combination was stimulatory in both stages. The retinoic acid in this combination may be of importance in the regulation of PA secretion by seminiferous tubules.
 ...
PMID:Regulation of stages VI and VIII of the rat seminiferous epithelial cycle in vitro. 370 Dec 34

Although treatment of cultured granulosa cells with gonadotropins increases their fibrinolytic activity, the biochemical nature of this effect is unclear. We have used sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fibrin autography techniques to characterize the fibrinolytic components secreted by granulosa cells. The fibrinolytic activity of these cells results from the production of both a tissue-type plasminogen activator (t-PA) and a urokinase-like activator (u-PA). The cells also produce an inhibitor of fibrinolysis (antiactivator). FSH and LH stimulate t-PA activity and suppress antiactivator activity, while u-PA activity is not affected by the gonadotropins. The differential regulation of these molecules by the gonadotropins may be essential for ovulation.
 ...
PMID:Cultured granulosa cells produce two plasminogen activators and an antiactivator, each regulated differently by gonadotropins. 391 58

Fibrinolytic activity in porcine follicular fluid and plasminogen activator production by porcine granulosa cells in response to gonadotropins is described. Fibrinolytic activity was determined using a solid phase assay in which 125I-fibrinogen was coupled to latex beads. Urokinase plus plasminogen served as the standard. Porcine follicular fluid contained protease inhibitors as evidenced by its ability to inhibit the activity of an urokinase-plasminogen standard. Removal of these inhibitors by acid precipitation revealed plasminogen-dependent and -independent fibrinolytic activity. Cultured granulosa cells produced plasminogen activator in amounts that increased over time. This pattern was most significant in cells stimulated by hCG. Cells incubated with hCG produced significantly more plasminogen activator when compared to those cells cultured in absence of gonadotropin. The enhancement was most marked during the second 48 hrs in culture (p = 0.032). FSH was found to have no stimulatory effect on plasminogen activator production by cultured porcine granulosa cells.
 ...
PMID:Porcine granulosa cell production of plasminogen activator: disparity between the effects of hCG and pFSH. 393 84

Tissue type (t) and urokinase type (u) plasminogen activators (PA) have been shown to be secreted by Sertoli cells in the seminiferous tubules in a cyclic fashion and to be dependent upon hormonal stimulation or the presence of adjacent spermatogenic cells. Furthermore, in cultured Sertoli cells, tPA has been shown to respond to FSH induction whereas uPA appears to be nonresponsive to gonadotropins. In the present study we analyzed the production of PA by Sertoli cells and regulation of this production by FSH during puberty. Cultured Sertoli cells under basal conditions secreted predominantly uPA. This production was high in 10-day-old animals and gradually decreased in older animals. The treatment of cultures with FSH or dibutyl cAMP induced production of tPA by Sertoli cells but at the same time produced a decrease in uPA activity. Northern blot analysis revealed that the control of PA synthesis is at the steady-state level of their mRNAs. Moreover, the use of cycloheximide, a protein synthesis inhibitor, showed that while tPA stimulation did not require intermediary protein synthesis, the decrease in uPA production was dependent upon protein synthesis. The differences in PA production by Sertoli cells obtained after FSH stimulation could explain the cyclic production of the two enzymes during the spermatogenic cycle and reinforce the hypothesis that different roles are played by the two enzymes in the several events occurring in testis development.
 ...
PMID:Hormonal regulation of urokinase- and tissue- type plasminogen activator in rat Sertoli cells. 754 41

We investigated the effect of gonadotropins on protease that were suggested to be implicated in the invasive activity of the trophoblast. hCG levels ranging from 10 x 10(3) to 333 x 10(3) IU/L produced a dose-dependent inhibition of the in vitro globinolytic activity of the purified proteases trypsin, chymotrypsin, and urokinase, but failed to inhibit plasmin, collagenase, elastase, and tissue-type plasminogen activator. Likewise, FSH inhibited purified trypsin and urokinase, but not plasmin or tissue-type plasminogen activator. Culture medium conditioned with human trophoblast displayed serine protease and urokinase-like activities; exposure of the cultured trophoblast to exogenous hCG markedly suppressed serine protease and urokinase activities in the conditioned medium. A short treatment of the conditioned medium with trypsin abolished the hCG-mediated inhibition of urokinase activity. The present findings offer an explanation for earlier observations that hCG reduced collagenase activity in trophoblasts without affecting the level of collagenase-specific mRNA. The present results are also consistent with the concept that hCG, by its direct ability to inhibit certain serine proteases and urokinase in trophoblast, suppresses a protease-mediated conversion of procollagenase to active collagenase. The ability of hCG to prevent initiation of the collagenolytic cascade suggests that gonadotropins may regulate the transient invasive activity of the trophoblast.
 ...
PMID:Gonadotropin-mediated inhibition of proteolytic enzymes produced by human trophoblast in culture. 768 89

In the present study, we have examined the influence of transforming growth factor-alpha (TGF alpha) and FSH in vitro on the granulosa cell plasminogen activator (PA) system accompanying cell proliferation and differentiation during follicular development. Undifferentiated and differentiated rat granulosa cells from diethylstilbestrol (DES)- and eCG-treated immature rats, respectively, were cultured in medium containing FSH (400 ng/ml), TGF alpha (0.5-50 ng/ml), and/or transforming growth factor-beta (TGF beta; 25-100 ng/ml). Net secreted PA (PAs) and cell-associated PA (PAc) activities were higher in differentiated cells and were stimulated by TGF alpha (but not by TGF beta) in a concentration-dependent manner. Basal and FSH-stimulated PAs was higher than PAc and accounted for 70-80% of the total PA activity in both cell preparations. FSH-stimulated PA activities increased in undifferentiated granulosa cells but decreased in differentiated cells with increased duration of culture. A biphasic effect (stimulatory in the first 24 h and inhibitory thereafter) of TGF alpha on FSH-induced PA activities was observed in the cultures of undifferentiated granulosa cells. Whereas both urokinase (uPA) and tissue (tPA) PA appeared to be present in cultures of granulosa cells from DES-treated rats, only tPA could be detected in those from eCG-treated animals. TGF alpha increased basal tPA activity at both stages of follicular development but inhibited activities of uPA in undifferentiated granulosa cells, irrespective of the presence of FSH. This growth factor stimulated basal progesterone (P) and 20 alpha-dihydroprogesterone (20 alpha-OH-P) secretion (an index of granulosa cell differentiation), the effect being more pronounced at the late stage of follicular development.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Follicular stage-dependent regulation of rat granulosa cell plasminogen activator system by transforming growth factor-alpha in vitro. 771 Dec 10

The objective of the present in vitro study was to examine the potential modulatory influence of tumor necrosis factor-alpha (TNF alpha) on the granulosa cell plasminogen activator (PA) system during follicular development. Undifferentiated and differentiated rat granulosa cells of preantral follicles and antral follicles, respectively, were cultured in a chemically defined medium with or without TNF alpha and in the absence or presence of FSH (400 ng/ml). TNF alpha (0.5-50 ng/ml) inhibited basal and FSH-induced net PA activities in cultures of granulosa cells from preantral and antral follicles in a concentration- and time-dependent manner. Although PA activities with corresponding molecular masses of 55 kDa and 30 kDa (tissue-[tPA] and urokinase-[uPA] type PA, respectively) were observed in culture of undifferentiated granulosa cells, only tPA was detectable in differentiated cells. Concomitant to the stimulation in PA activities by FSH was a marked increase in progestin secretion and a decrease in DNA synthetic capacity at both stages of follicular development. Independent of the differentiative state of the granulosa cells, TNF alpha suppressed FSH-stimulated tPA activity, but potentiated FSH-induced uPA activity in undifferentiated granulosa cells. The inhibition of the gonadotropin action by TNF alpha was accompanied by an increase in PA inhibitor activity, which was more pronounced in cultures of differentiated granulosa cells. TNF alpha inhibited FSH-induced progestin secretion and reversed the action of the gonadotropin on DNA synthesis irrespective of stage of follicular maturation. These studies demonstrate that TNF alpha modulates gonadotropic action on granulosa cell differentiation (PA and progestin secretion) and proliferation (DNA synthesis) during follicular development.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tumor necrosis factor alpha inhibits rat granulosa cell plasminogen activator activity in vitro during follicular development. 777 96

Following the preovulatory surge of gonadotropins, the compact layer of cumulus cells in the antral follicle secretes a hyaluronic acid-enriched extracellular matrix and undergoes a morphological change referred to as cumulus expansion. It has been previously shown that a soluble factor(s) produced by the oocyte is required, in combination with FSH, to promote this process. Since such matrix is sensitive to proteases we have now studied the effect of the oocyte on another gonadotropin-controlled follicle cell function, i.e., the synthesis of plasminogen activator (PA). Our data indicate that isolated cumulus cells secrete uPA in the medium and that FSH or dbcAMP increases this production. The presence of the oocyte or the oocyte-conditioned medium greatly reduces uPA synthesis induced by FSH and dbcAMP in cumulus cells by modulating the abundance of its mRNA. The ability of the mouse oocyte to produce such a factor(s) is dependent upon its stage of development, with fully grown oocytes but not growing oocytes or two-cell embryos being able to inhibit uPA synthesis. A preliminary characterization of this factor suggests that it is a heat-unstable protein with an apparent molecular weight above 100 kDa. Thus, the mouse oocytes appear to promote preovulatory matrix accumulation that occurs just prior ovulation by modulating the gonadotropin action on both the synthesis and the degradation of specific matrix component.
 ...
PMID:Mouse oocytes inhibit plasminogen activator production by ovarian cumulus and granulosa cells. 785 58

We have demonstrated for the first time that (i) mouse Sertoli cells predominantly secrete tPA under the action of FSH and cAMP-generating agents, whereas Leydig cells mainly produce uPA; (ii) Sertoli cells are also capable of secreting PAI-1, as well as FSH, growth factors and GnRH increase PAI-1 gene expression; (iii) the increases in tPA and PAI-1 activities by different hormones in the conditioned media of Sertoli cells correspond to the increases in the levels of tPA and PAI-1 mRNA in the cultured cells, suggesting that the synthesis of the activator-inhibitor in mouse Sertoli cells is regulated at a transcriptional level and the tPA secreted by Sertoli cells may be involved in the spermatogenesis.
 ...
PMID:Hormonal regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 gene expression in cultured mouse Sertoli cells. 839 3

Tissue remodeling that accompanies ovarian follicular cell proliferation and migration during follicular maturation and ovulation involves enzymatic degradation of extracellular matrix by proteases such as plasminogen activator (PA). However, the potential role of interleukin-1 beta (IL-1 beta) in the regulation of the rat granulosa cell PA system during folliculogenesis is not known. In vitro treatment of both undifferentiated and differentiated granulosa cells with FSH (400 ng/ml) elicited a significant increase in secreted (PAs) and cell-associated (PAc) PA activities, which were inhibited by IL-1 beta (0.5-50 ng/ml) in a concentration- and time-dependent manner. Basal PAs and PAc activities were stimulated in cultures of undifferentiated granulosa cells by IL-1 beta but attenuated in differentiated ones. The inhibitory effect of IL-1 beta was accompanied by an increase in PA inhibitor (PAI) activity irrespective of the stage of follicular development. Both urokinase-type PA (uPA; 30 kDa) and tissue-type PA (tPA; 55 KDa) activities were present in cultures of undifferentiated granulosa cells, but only tPA was detectable in differentiated granulosa cell cultures. Activity of both enzymes was stimulated by FSH but inhibited by the cytokine in vitro. Whereas FSH-induced differentiation of granulosa cells as indicated by an increase in progesterone (P) secretion was attenuated by IL-1 beta irrespective of the cytodifferentiative state of granulosa cells, the inhibitory effect of gonadotropin on DNA synthesis was reversed by the cytokine at both stages of follicular maturation. These findings suggest that during ovarian folliculogenesis, IL-1 beta may modulate the progression of granulosa cells from a proliferative to a differentiated state and may play a control role in determining the fate of the follicle (i.e., ovulation vs. atresia).
 ...
PMID:Regulation of rat granulosa cell plasminogen activator system: influence of interleukin-1 beta and ovarian follicular development. 856 85


<< Previous 1 2 3 Next >>