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)

The plasminogen activator/plasmin synthetic substrate S-2251 was used to measure the effect of indomethacin, cycloheximide, colchicine, dexamethasone, tranexamic acid, and aprotinin on the elevation of ovarian plasminogen activator (PA) that normally occurs during ovulation in the rat. Young Wistar rats were weaned on the morning of Day 21, given 4.0 IU of pregnant mare's serum gonadotropin (PMSG) s.c. at 0800 h on Day 22, and given 10.0 IU of human chorionic gonadotropin (hCG) on Day 24. These animals normally began ovulating between 0000 and 0200 h on Day 25. The induced ovulation rate was 11.5 +/- 2.2 ova/rat, based on the number of ova in the oviducts of control animals at 0900 h on Day 25. In the controls, PA activity in extracts of homogenized ovaries increased 3-fold from 0.125 +/- 0.010 OD units just before the administration of hCG to 0.371 +/- 0.021 at 12 h after hCG, i.e., near the time of ovulation. Indomethacin, in doses of 0.1-1.0 mg/rat, inhibited ovulation but did not inhibit the normal increase in PA activity, whereas indomethacin at the high dose of 10.0 mg/rat inhibited both ovulation and PA activity. Cycloheximide, at a dose of 0.1 mg/rat, was given at 12 h before hCG, immediately after hCG, and at 9 h after hCG. This agent inhibited ovulation most effectively when given at 12 h before hCG, yet it inhibited PA activity most effectively when given immediately after or at 9 h after hCG. Colchicine, at a dose of 0.1 mg/rat, inhibited ovulation, but not PA activity, when it was given 1 h before hCG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of various agents on ovarian plasminogen activator activity during ovulation in pregnant mare's serum gonadotropin-primed immature rats. 241 37

The observation that tissue-type plasminogen activator (tPA) activity increased dramatically in preovulatory follicles has led to the hypothesis that plasminogen activation is causally related to follicle rupture. With immunohistochemistry, we have studied the appearance of tPA in ovaries of immature rats induced to ovulate and in adult cycling rats. Treatment of immature female rats with a single dose of pregnant mare serum gonadotropin (PMSG) induced follicular maturation. A subsequent human chorionic gonadotropin (hCG) injection resulted in follicle rupture 12-14 h later. PMSG treatment alone did not induce appearance of tPA-immunoreactive cells in any ovarian compartment. After hCG stimulation, however, theca cells, granulosa cells, and oocytes of pre- and postovulatory follicles displayed distinct tPA immunoreactivity. Fibroblast-like cells in the theca layers and tunica albuginea of the follicle apex also demonstrated localized cytoplasmic tPA reactivity. In addition to tPA synthesis in preovulatory follicles, hCG also induced tPA staining in the theca (but not granulosa) layers of non-ovulatory follicles. At 24 h after hCG treatment, there was a marked tPA staining in developing corpora lutea, ovulated ova, and oviductal epithelium. Ovaries from regularly cycling adult rats displayed a similar ovulation-related pattern of tPA immunostaining. The appearance of tPA in different cell types of the preovulatory follicle and in the fibroblast-like cells at the follicle apex, strengthens the hypothesis of a direct involvement of tPA in follicle rupture. Presence of tPA in postovulatory oocytes, cumulus cells, and surrounding oviductal epithelium may also indicate a role for tPA in the transfer of eggs in the oviduct.
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PMID:Immunohistochemical localization of tissue-type plasminogen activator in ovaries before and after induced and spontaneous ovulation in the rat. 250 12

To assess the role of inhibitors of proteolytic enzymes, such as plasminogen activator (PA) and collagenase in the ovulatory process, inhibitor activity and mRNA levels were examined in periovulatory rat and human ovaries. In the rat, immature animals received 20 IU of pregnant mare serum gonadotropin (PMSG) followed 52 h later by 10 IU of hCG. Ovaries were removed at intervals from 0 to 20 h after human chorionic gonadotropin (hCG) administration. Inhibitor activity for metalloproteinases, such as collagenase, increased from 60.5 +/- 4.1 inhibitor units/ovary at 0 h (i.e., time of hCG treatment) to a maximum of 218.2 +/- 11.4 units/ovary at 8 h after hCG before decreasing at 12 h (time of ovulation) and 20 h (122.2 +/- 7.9 and 71.6 +/- 8.1 units/ovary, respectively). Human follicular fluid and granulosa cells were obtained from preovulatory follicles of patients in our in vitro fertilization program. Metalloproteinase inhibitor activity was evaluated in follicular fluid as well as the levels of PA and PA inhibitor (PAI) mRNA by Northern analysis. Increasing metalloproteinase inhibitor activity was positively correlated with follicular levels of estradiol (p less than 0.001) and progesterone (p less than 0.02, N = 26). Chromatographic separation of follicular fluid resulted in two peaks of metalloproteinase inhibitor activity. The large molecular weight (MW) inhibitor had an approximate size of 700 kilodaltons (kDa) and may represent alpha 2-macroglobulin, a serum-derived inhibitor. The small MW inhibitor shared many of the characteristics of tissue-derived inhibitors of metalloproteinases. Partial purification of the small MW inhibitor by Concanavalin A-Sepharose and Heparin-Sepharose chromatography demonstrated the inhibitor to be a glycoprotein with an approximate MW = 28-29 K. Northern analysis of human granulosa cell total RNA from preovulatory follicles showed little or no detectable tissue-type PA or urokinase-type PA mRNA. In contrast, two species of PA inhibitor type-1 mRNA were detected in relative abundance. The present findings demonstrate the presence of proteolytic inhibitors in periovulatory ovaries of the rat and human. These ovarian inhibitors may play a role in regulating connective tissue remodeling during follicular rupture.
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PMID:The role of ovarian proteases and their inhibitors in ovulation. 255 99

During ovulation, enzymatic degradation of the extracellular matrix occurs within and around the graafian follicles. In this study, the activities of several different proteolytic enzymes were measured in the culture media of follicles taken from pregnant mare serum gonadotropin (PMSG)-primed immature rats. At 52 h after PMSG, the follicles were cultured for 2 to 15 h in media with or without human chorionic gonadotropin (hCG). Type I collagenase activity in hCG-stimulated follicles gradually increased within 6 h to 3.3-fold above that of the controls. Relatively pure populations of granulosa cells produced type I collagenase to a similar extent. Likewise, type IV collagenase increased 3.8-fold by 6 h after exposure of the follicles to hCG. In contrast, plasminogen activator activity increased by 3.9-fold at 2 h after hCG, but was negligible at 4, 6, and 15 h after incubation. These results suggest that plasminogen activator may activate both type I and type IV collagenase in hCG-stimulated ovulatory follicles.
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PMID:Types I and IV collagenolytic and plasminogen activator activities in preovulatory ovarian follicles. 303 95

Two types of plasminogen activator (tissue-type, tPA; urokinase-type, uPA) have been demonstrated in ovarian granulosa cells, but only tPA activity was found in denuded oocytes. Immature rats were treated subcutaneously with 20 IU pregnant mare's serum gonadotropin (PMSG) to stimulate follicle maturation, followed 2 days later by an injection of 10 IU human chorionic gonadotropin (hCG) to induce ovulation. Cellular plasminogen activator activities were determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis followed by a fibrin-overlay technique. Cumulus-oocyte complexes from rats before and after PMSG treatment contained low amounts of tPA, but not uPA, activity. After hCG treatment, tPA activity showed a time-dependent increase, reaching a maximum at 24 h after injection. At 12 and 24 h after hCG treatment, uPA activity was also detected. The appearance of high molecular weight lysis zones further suggested the formation of plasminogen activator-inhibitor complexes. Morphological analysis indicated that the increases in oocyte tPA activity were correlated with the extent of cumulus cell expansion and dispersion. In denuded oocytes, tPA activity also progressively increased during the periovulatory period to a maximum at 24 h after hCG treatment. In contrast, neither uPA activity nor activator-inhibitor complex was detected. Secretion of the proteases was measured in the conditioned media of cumulus-oocyte complexes cultured for 24 h in vitro. Substantial increases in tPA release were found in complexes obtained at 8 and 12 h after hCG injection, with lower secretion from complexes obtained at 24 h after hCG treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasminogen activator activity in cumulus-oocyte complexes of gonadotropin-treated rats during the periovulatory period. 310 10

In vivo and in vitro studies were performed to determine the function of Leydig and Sertoli cells of the human testis with various degrees of spermatogenic impairment. The increases in basal and peak serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) after LH-RH administration correlated with the degree of impairment of spermatogenesis, and the basal peripheral blood levels of testosterone and that after human chorionic gonadotropin (hCG) administration for patients with moderate or severe impairment were significantly lower than the values for those with mild impairment. The concentration of testosterone in the internal spermatic vein of varicocele patients with or without hCG treatment did not differ between in mild and moderate impairment. In studies on cultured Sertoli cells, the production rate of plasminogen activator in patients with severe impairment was significantly lower than that in patients with moderate or mild impairment. The decrease in testicular high-affinity binding site for FSH correlated with the degree of hypospermatogenesis found in idiopathic male infertility, but, on the contrary, the hCG (LH) receptors showed no correlation with the degree of impairment of spermatogenesis. In the investigation of the relationship between testicular FSH receptors and the effectiveness of human menopausal gonadotropin (hMG)-hCG treatment on idiopathic male infertility, the presence or absence of testicular FSH receptors predicted the responsiveness to the treatment.
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PMID:[Endocrinological profile of human spermatogenic impairment--evaluation of function of Leydig and Sertoli cells in vivo or in vitro studies]. 314 48

Eight independent cell lines, derived from human testicular germ-cell tumors, were examined for the expression of various markers. These included major histocompatibility and embryonic antigens, chorionic gonadotropin, alpha fetoprotein, alkaline phosphatase, plasminogen activator, and infectivity by SV40. No line consisted primarily of choriocarcinoma or yolk sac cells, but several contained cells resembling murine embryonal carcinoma; some of these lines formed tumors with the distinctive features of embryonal carcinoma when injected into immunosuppressed animals. It is proposed that human embryonal carcinoma cells, unlike those of the mouse, correspond to a preblastocyst stage of development.
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PMID:A comparative study of eight cell lines derived from human testicular teratocarcinoma. 616 54

In the five kinds of human cultured cells derived from ovarian adenocarcinoma (HOC-21), ovarian malignant teratoma (HOTC 3), carcinoma of the uterine endometrium (HEC-1B), squamous cell carcinoma of the uterine cervix (SKG-1) and choriocarcinoma (BeWo), the intracellular presence of lactic dehydrogenase (LDH), alkaline phosphatase (AlP), human chorionic gonadotropin (HCG), alpha-fetoprotein (AFP) and plasminogen activator were investigated. The results were as follows. 1) BeWo-, HOC-21-and HOTC 3-cells revealed high activity of intracellular presence of lactic dehydrogenase (LDH), alkaline phosphatase (AlP), human chorionic gonadotropin (HCG), alpha-fetoprotein (AFP) and plasminogen activator were investigated. The results were as follows. 1) BeWo-, HOC-21-and HOTC 3-cells revealed high activity of intracellular LDH in this order, however none of HEC-1B-and SKG-1-cells did. 2) The activity of intracellular AlP was higher in BeWo-cells than in HOC-21-cells. The isozymes of AlP detected in these cells were found to be heat-stable. The others revealed no activity of AlP. 3) The presence of HCG-beta was confirmed in both BeWo- and HOTC 3-cells. The intracellular levels of HCG-beta were found to be higher in BeWo- cells than in HOTC 3-cells. HCG-beta was observed to leak into culture medium not from HOTC 3-cells but from BeWo-cells. It was not detected in the other cultured cells. 4) No AFP was detected in any of these five cultured cells. 5) Plasminogen activator was detected in HOC-21, HEC-1B-and SKG-1-cells in contrast to HOTC 3-and BeWo-cells which were negative for plasminogen activator. These results suggest that the various marker substances detected in the human cultured cells originated from various carcinomas of sexual organs may reflect biological functions of these tumor cells and, furthermore, can apply as tumor markers to the clinical diagnosis of the diseases.
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PMID:[Studies on marker substances in cell lines derived from various human gynecologic tumors (author's transl)]. 617 49

Sertoli cells in primary cultures produce plasminogen activator activity, and release it into the medium at rates greatly influenced by a variety of factors, including cell density, the presence of hormones, incubation temperature and duration of culture. In Sertoli cells maintained in culture in the presence of dibutyryl cAMP, the amounts of plasminogen activator activity secreted per cells were maximal at cell densities up to 2.5 microgram DNA/cm2 (350 units/microgram cell DNA), and declined to 40 units/microgran cell DNA at a density of 22 micrograms DNA/cm2. Concentrations of follicle-stimulating hormone (FSH) required to elicit half-maximal stimulation of the production of plasminogen activator activity were 0.37 micrograms/ml for oFSH-NIH S12 and 8 ng/ml for the more purified of SH-S1528C2. The ED50 for dibutyryl cAMP was found to be 0.08 mM. Addition of an inhibitor of phosphodiesterase (3-isobutyl-l-methylxanthine) enhanced the formation of plasminogen activator by cells cultured in the presence of FSH. Addition to the culture medium of testosterone, epidermal growth factor, insulin, human chorionic gonadotropin or prostaglandins (E1, E2 or F1 alpha) did not result in increased production of PA activity by Sertoli cells. Cells in culture for as long as 14 days remained responsive to FSH or dibutyryl cAMP. Increases in cellular levels of plasminogen activator became evident within 2-4 after addition of either FSH or dibutyryl cAMP to the medium. The stimulation of FSH or dibutyryl cAMP of the production of plasminogen activator activity was shown to be dependent upon de novo synthesis of RNA and protein. Levels of enzyme activity released by Sertoli cells maintained in culture for 48 h at 37 degrees C were approx. 50% higher than plasminogen activator released by cells cultured at 32 degrees C. The control of the production of plasminogen activator activity by Sertoli cells was discussed in relation to the control of plasminogen activator production by granulose cells, and the possible role of plasminogen activator in gonadal functions.
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PMID:The control of the synthesis and secretion of plasminogen activator by rat sertoli cells in culture. 617 77

Recently, it has been shown that granulosa-cell secretion of plasminogen activator (PA) is responsive to luteinizing hormone (LH)/human chorionic gonadotropin (hCG) as well as follicle stimulating hormone (FSH) in the rat and the pig. Accordingly, we asked whether PA activity in follicular fluid from exogenously stimulated human follicles was different from that of normal cycles and whether or not these activities correlated with follicular maturation as determined by follicular fluid steroid concentration. Follicular aspirates were obtained from women who were participating in an in vitro fertilization protocol. Follicular fluid concentrations of estradiol and progesterone were determined by established radioimmunoassay. PA activity, determined using a modified indirect solid-phase radioassay, was significantly less in follicles from patients treated with human menopausal gonadotropin (hMG) plus clomiphene (P less than 0.05) compared to untreated patients or those receiving hMG or clomiphene alone. Correlations of PA activity and follicular fluid steroid concentrations demonstrated no significant correlation in samples from treated patients. In contrast, untreated spontaneously cycling patients had a significant (r = 0.89, P less than 0.05), positive correlation between follicular fluid estradiol levels. There was no correlation between PA activity and follicular fluid progesterone levels in any of the groups. These results suggest that a subtle balance in granulosa-cell secretion of PA and steroid exists, which appears to be disrupted by follicular hyperstimulation during treatment of patients participating in in vitro fertilization protocols.
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PMID:Alteration of human follicular fluid plasminogen activator activity by ovarian hyperstimulation. 644 21


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