Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two types of plasminogen activator (PAs) are present in human endometrium, and their contents vary with the different phases of menstrual cycle, i.e. high in the proliferative phase and low in the secretory phase. In the present study by immunohistochemical technique, both uPA and tPA antigens were demonstrated in the stromal and glandular cells of the endometrium. In cell culture, tPA was released only from stromal cells and uPA only from glandular cells as determined by SDS-PAGE followed by fibrin overlay technique, but PA inhibitor type-1 (PAI-1) was secreted by both stromal and glandular cells. Furthermore, secretion of PAs from endometrial cells was enhanced by adding estradiol and markedly inhibited by progesterone in a dose dependent manner, while the PAI reacted just in the opposite way. The effect of the peptide hormones, hCG, GnRH, PRL, as well as cAMP in cell culture on the secretion of PAs and PAI was similar to that of estradiol, while forskolin demonstrated definitely more stimulative effect on tPA than uPA. Taking into account of the finding of the present study, it appears that, under hormonal control, a balance between PAs and PAI in the endometrium exists. The physiological roles of the PAs and PAI in the endometrium were discussed.
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PMID:[Plasminogen activators and plasminogen activator inhibitor type-1 in human endometrium]. 129 66

The present study was undertaken to evaluate the effects of PRL in the process of ovulation and oocyte maturation. In the first experiment, using an in vitro perfused rabbit ovary model, the addition of PRL to the perfusate inhibited hCG-induced ovulation in a dose-related fashion, without any reduction in progesterone synthesis. In a subsequent experiment, PRL directly inhibited both the degeneration and decomposition of surface epithelial cells and the disruption of connective tissue at the apex of the follicle wall. Furthermore, PRL inhibited hCG-stimulated plasminogen activator (PA) activity in mature follicles in a dose-related fashion. In the final experiment, we demonstrated conditions in which rabbit oocytes matured in vitro acquire competence for early embryonic development. PRL, as well as gonadotropins and estradiol, was an important constituent in the process of oocyte maturation, promoting embryonic development. These results suggest that the preovulatory environment of PRL within the follicle may influence the process of ovulation and oocyte maturation.
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PMID:Possible contribution of prolactin in the process of ovulation and oocyte maturation. 175

The present study was designed to determine the effects of PRL on changes in morphology and plasminogen activator (PA) activity in the preovulatory follicles. Rabbit ovaries were perfused with hCG alone or with hCG plus at 10, 10(2), or 10(3) ng/ml. PRL at 10(3) ng/ml directly inhibited the degeneration and decomposition of surface epithelial cells induced by hCG exposure. The subsurface connective tissue was visualized by treatment with sodium dodecyl sulfate, which removed surface epithelial cells from the ovary, thereby exposing collagen fibrils and the basal lamina. Sodium dodecyl sulfate treatment revealed inhibition of connective tissue disruption at the apex of the follicle wall in PRL-treated ovaries. PA activity in mature follicles in perfused rabbit ovaries exposed to hCG increased from 1.40 +/- 0.08 to 28.4 +/- 4.25 IU/g tissue after 4 h of perfusion. The addition of PRL to the perfusate inhibited the hCG-stimulated increase in intrafollicular PA activity in a dose-dependent fashion. Although at 7 h mature follicles treated by hCG alone showed greater intrafollicular PA activity than those treated with hCG plus PRL, this difference was not significant. These results suggest that PRL may act directly by interfering with mechanical events within the ovary that are required for the rupture of mature Graafian follicles, probably via the inhibition of intrafollicular tissue PA activity.
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PMID:Prolactin inhibits plasminogen activator activity in the preovulatory follicles. 229 9

The purpose of this study was to adduce further evidence for a paracrine role for human decidual relaxin (Rlx) in the remodelling of collagen in the fetal membranes in the peripartal period. The binding of [125I]porcine Rlx to membrane-enriched fractions from fetal membranes as well as from dispersed cells from the fetal membranes was used to demonstrate the presence of specific Rlx receptors. Rlx added in vitro to cultured amnion/chorion cells increased the release of plasminogen activator and collagenase into the medium. Rlx had no effect on the release of beta-glucuronidase. An in vivo correlate of these in vitro results was obtained, the detection of plasminogen activator and collagenase in amniotic fluids. The active fraction of collagenase was increased in amniotic fluids collected after spontaneous rupture of the membranes. PRL, hCG, estrogen, and progesterone added in equimolar amounts to cultured amnion/chorion cells from elective cesarean sections and normal term deliveries also effected the release of plasminogen activator and collagenase. The greatest effects were found in cells from cesarean section tissue, in terms of the stimulation of plasminogen activator release by Rlx and PRL and of collagenase release by prostaglandin F2 alpha and, to a lesser extent, by Rlx, PRL, and hCG. We conclude that human fetal membranes are targets for a number of hormones, including the decidual paracrine hormones Rlx, PRL, and prostaglandin F2 alpha as well as estrogen, progesterone, and hCG. These hormones act to release or inhibit the enzymes involved in collagen breakdown before rupture of the fetal membranes.
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PMID:The human fetal membranes: a target tissue for relaxin. 300 43

The role of FSH in the regulation of plasminogen activator production was studied in granulosa cells obtained from 23- to 25-day-old female rats. Cells cultured without FSH secreted a negligible amount of plasminogen activator. Purified ovine, rat, and human FSH produced dose-dependent increases in plasminogen activator production. This FSH effect was mimicked by analogs of cAMP, prostaglandin E2, and choleratoxin. Purified ovine LH and ovine PRL had no effect on plasminogen activator production by these immature granulosa cells. However, when these granulosa cells were treated in vitro or in vivo with FSH and then exposed to LH or PRL, the cells responded to LH in a dose-dependent manner with increased plasminogen activator production. These cells remained unresponsive to PRL. Similarly to FSH, in vitro pretreatment of the cells with choleratoxin or analogs of cAMP also induced responsiveness to LH with increased plasminogen activator production. This responsiveness to both FSH and LH with increased plasminogen activator production was also observed in granulosa cells obtained from rat preovulatory follicles. These studies demonstrate that: 1) FSH but not LH regulates plasminogen activator production by immature granulosa cells from preantral follicles; 2) Pretreatment of the undifferentiated granulosa cells with FSH, choleratoxin, or cAMP induced granulosa cell responsiveness to LH with increased plasminogen activator production; and 3) Granulosa cells obtained from preovulatory follicles respond to both FSH and LH with increased plasminogen activator secretion. These results suggest that with the LH surge at ovulation, plasminogen activator production in follicles is increased and may be important in follicular rupture.
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PMID:Gonadotropins regulate plasminogen activator production by rat granulosa cells. 629 87

We have demonstrated in this study that prolactin inhibits hCG-induced ovulation in PMSG-primed mice. At 18 h after the hormone treatment the number of ova in the oviducts was found to be 31.7 +/- 6.7 (mean +/- SE) in hCG treated group. The number was significantly decreased (19.7 +/- 4.9) when 100 micrograms of prolactin was injected simultaneously. The same effect of PRL on hCG induced ovulation could be also observed at 24 h after the hormone treatment; the values reached respectively to 32.3 +/- 10.8 and 20.3 +/- 5.4. Both in vivo and in vitro experiments further showed that the inhibition of the gonadotropin-induced ovulation by PRL is mediated through decreasing in the ovarian plasminogen activator activity.
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PMID:[Prolactin inhibits gonadotropin-induced increase in ovarian plasminogen activator activity and ovulation in mouse]. 814 75

During in vitro decidualization of human endometrial stromal cells (HESCs), medroxyprogesterone acetate (MPA) inhibits expression of the potent extracellular matrix (ECM)-degrading protease stromelysin-1 (MMP-3), but enhances PRL expression. Consistent with its priming role in vivo, estradiol (E2) augments these effects. In the current study, immunoblot analysis revealed that coincubation with 10(-6) M RU 486 blocked the inhibition in HESC-secreted MMP-3 levels (50,000 mol wt) evoked by 10(-8) M E2 + 10(-7) M MPA. Although MPA can act as a glucocorticoid, the HESCs were refractory to 10(-7) M dexamethasone added alone or with E2. Because E2 elevates progesterone but not glucocorticoid receptor levels, MPA and RU 486 control MMP-3 expression as a progestin and antiprogestin, respectively. To study RU 486 involvement in steroid withdrawal leading to menstruation, HESCs were decidualized during 10 days incubation with E2 + MPA, and parallel cultures were kept in E2 + MPA or withdrawn to either control or RU 486-containing medium. Compared with E2 + MPA-suppressed HESCs, increases in levels of secreted MMP-3 (2.0-fold), and its 2.1-kilobase messenger RNA (10-fold) were observed in HESCs after 4 days of withdrawal to control medium, with much greater increases seen in RU 486-containing medium (10-fold protein, 100-fold messenger RNA). Previously, we showed that RU 486 up-regulated E2 + MPA-inhibited plasminogen activator expression in the cultured HESCs. Extrapolation of these in vitro observations to endometrial events following RU 486 administration suggests that coordinate enhancement of MMP-3 and plasminogen activator expression promotes proteolysis of the stromal/decidual ECM, which leads to endometrial sloughing. Moreover, destabilization of endometrial microvessels resulting from degradation of their surrounding ECM is consistent with the heavy menstrual bleeding stemming from RU 486 administration. However, in contrast to the marked RU 486-initiated reversal of MMP-3 expression, RU 486 did not significantly reverse E2 + MPA-enhanced PRL secretion by the cultured HESCs. Interestingly, decidual PRL, unlike decidual MMP-3, does not appear to play a role in menstruation. Interleukin-1 beta counteracted E2 + MPA-mediated inhibition of secreted MMP-3 levels, implying that leukocyte/trophoblast-derived cytokines can modulate steroid-regulated MMP-3 expression by stromal/decidual cells during menstruation and pregnancy.
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PMID:Biological mechanisms underlying the clinical effects of RU 486: modulation of cultured endometrial stromal cell stromelysin-1 and prolactin expression. 898 57

The N-terminal fragment of PRL (16K PRL) is an antiangiogenic factor that, in vitro, inhibits several components of angiogenesis including basic fibroblast growth factor (bFGF)-induced cell division, migration, and organization of capillary endothelial cells. An essential step in the regulation of angiogenesis is the activation of urokinase (urokinase type plasminogen activator, uPA), which in turn activates a cascade of proteases that play essential roles in endothelial cell migration and tissue remodeling. Treatment of bovine capillary endothelial cells (BBEC) with 16K PRL inhibited bFGF-stimulated urokinase activity in BBEC as detected by plasminogen substrate gel assay. 16K PRL did not appear to be acting via an effect on uPA expression because no change in messenger RNA levels were observed. However, protein levels of plasminogen activator inhibitor-1 (PAI-1), a specific inhibitor of urokinase, were increased by 16K PRL independent of the action of bFGF. The 16K PRL-induced increase in PAI-1 protein levels appear to be the result of increased expression of the PAI-1 gene. Increased production of PAI-1 induced by 16K PRL results in the formation of inactive PAI-1/uPA complexes, consistent with the observed decrease in uPA activity.
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PMID:Inhibition of urokinase activity by the antiangiogenic factor 16K prolactin: activation of plasminogen activator inhibitor 1 expression. 972 20