Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy-five pregnant women in the 38th to 41st weeks of gestation were given a single intravenous injection of 200 mg of dehydroepiandrosterone sulfate (DHAS). The changes in estriol, 17beta-estradiol and progesterone levels in the serum, the uterine cervix and the myometrium of the placenta-implanting site were then determined. Estriol levels remained unchanged both in serum and tissue, but the level of 17beta-estradiol increased sharply both in serum and tissue after four hours. The increases of 17beta-estradiol in the serum and the portio vaginalis of the same patient were well correlated (r = 0.79898), but the percentage of increase was much higher in the portio vaginalis than in the serum (p less than 0.001). Serum progesterone levels did not change initially, but always decreased within four or eight hours in cases in which labor had started or delivery was accomplished within 24 hours (p less than 0.01 at four hours). The total amount of collagenase was determined in ten subjects before and after the administration of DHAS. The total collagenase activity was elevated by an average of 152.3%. The peak of activity was accelerated from the fourth to the second day (p less than 0.001) of the culture. A probable mechanism of DHAS action in accelerating cervical ripening is presented.
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PMID:Collagenolytic activity and steroid levels after administration of dehydroepiandrosterone sulfate. 3 88

Cervical biopsy specimens were obtained under standard conditions from the posterior lip of the uterine cervix in 105 patients. A significant increase of collagenase activity was observed during parturition as determined with an assay with iodine 125-labeled native triple-helical collagen type I as the substrate. The collagenase was not likely to originate from cervical fibroblasts because in situ hybridization failed to detect synthesis of the specific procollagenase messenger ribonucleic acid. However, migration of polymorphonuclear leukocytes into the cervical stroma occurred on onset of labor, and an antibody specific for human leukocyte collagenase that did not cross react with fibroblast collagenase revealed the presence of the enzyme in the granules of polymorphonuclear leukocytes and subsequently in the extracellular matrix of the cervix. Therefore it is likely that the cells critically involved in collagen degradation during cervical dilatation are not resident fibroblasts but rather polymorphonuclear leukocytes emigrating from blood vessels.
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PMID:Origin of cervical collagenase during parturition. 131 77

The ripening effect of dehydroepiandrosterone sulfate (DHA-S) on the uterine cervix was studied after intravaginal application. A 100-mg suppository containing 0, 5, 10 or 20% (w/w) DHA-S was applied to the vagina of pregnant rats 3 times on days 14-16 of gestation. Wet weight and water content of the uterine cervix increased dose-dependently. To measure the elasticity of the uterine cervix, the tension causing an expansion of 1 mm or 2 mm was determined; this was reduced by the application of 20% DHA-S, and the difference in the length of the cervix produced by tensions of 5 g and 25 g was increased. Application of 20% DHA-S decreased the collagen content of the uterine cervix and the total collagenase activity was increased. Furthermore, histochemical changes, coarsening and edema were observed in the uterine cervix. These findings suggest that intravaginal application of DHA-S would produce ripening effects similar to those after intravenous injection.
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PMID:[Pharmacological studies of intravaginally applied dehydroepiandrosterone sulfate (DHA-S)]. 165 59

Dilatation of the uterine cervix at parturition is accompanied by a remarkable alteration in its biomechanical characteristics leading to a significant reduction in its strength and stiffness. Our previous studies and those of others have suggested the involvement of collagenolysis leading to cervical dilatation. This study provides further evidence for the occurrence of collagenolysis in the dilated guinea pig cervix at birth. The changes in collagenase and collagenase inhibitory activity in vivo in cervices of nonpregnant, pregnant, and postpartum guinea pigs were determined. There were no significant changes in procollagenase, collagenase inhibitory activity, and net procollagenase in animals at 25 and 50 days of gestation compared with nonpregnant animals. At parturition (68 +/- 2 days), there was a 6-fold increase in procollagenase, a 26-fold increase in collagenase inhibitory activity, and a 2-fold increase in net procollagenase activity. Cervices in organ culture obtained at birth produced 2.9-fold more procollagenase, 1.6-fold more collagenase inhibitory activity, and a 10-fold increase in net procollagenase activity when compared to nonpregnant or 25-day pregnant animals. These studies indicate that dilatation of the guinea pig cervix at parturition involves collagenase-mediated degradation of collagen in the cervix.
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PMID:Biochemical evidence of collagenase-mediated collagenolysis as a mechanism of cervical dilatation at parturition in the guinea pig. 166 17

Changes in interstitial collagenase activity in the rat uterine cervix during ripening were clarified in a time-dependent manner. Premature delivery was induced by an antiprogesterone agent, RU486, for rats in late pregnancy. The presence of interstitial collagenase in the extract from the rat cervical tissue was demonstrated, by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis using the natural and unaffected collagen as a substrate. The collagenase activity was determined as the release of digested peptides from the radio-labeled collagen. Our experiments with RU486 were performed in rats on the 18th day of pregnancy. A single administration of RU486 (15 mg/kg) resulted in the premature delivery of all treated rats within 30 h after the injection (average time was 23.9 h). The marked increase in cervical wet weight was observed up to the time to premature delivery along with a significant acceleration from 18 h after the administration of RU486. In this state, the cervical collagenase activity was enhanced, the highest levels being recorded at 21 h after the administration. The interstitial collagenase in the uterine cervix appears to play a significant role in the regulation mechanisms of cervical ripening in late pregnant rats.
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PMID:Effects of RU486 on the interstitial collagenase in the process of cervical ripening in the pregnant rat. 184 68

Cervical ripening is reviewed from the viewpoint of mechanical properties, histological and biochemical structure of cervical tissue, and the role of hormones and other bioactive agents in the process. The uterine cervix begins abruptly with a 2-3 mm transition from the myometrium and is made of 80% type I collagen and 20% type III collagen fibers covalently cross linked, and glycosaminoglyucans covalently bound to protein cores. During pregnancy the collagen concentration is halved and its extractability increases due to changes in the proteoglycan composition, an increase in acidic relative to neutral proteins. These changes are responsible for the softening of the cervix (Goodell's sign) and the isthmus (Hegar's sign). Histologically the collagen fibers appear thinner and more spread out. Polymorphonuclear leukocytes and eosinophils may be involved in the softening process. Factors theorized or know to be involved in cervical ripening are progesterone, estradiol, prostaglandins (PGs), relaxin, and cytokines. Progesterone withdrawal has been shown in animal models. Estradiol either induces PG synthesis or sensitizes the cervix to locally produced PGs. PGE2 and PGF2alpha receptors have been found in cervical plasma membranes, have been isolated from tissue, their local synthesis can be manipulated, and their clinical use is well documented. Relaxin is a peptide synthesized in the corpus luteum, uterus and placenta, and is known to relax the pelvic girdle, restrain myometrial activity and soften the cervix. Cytokines such as interleukin-1 and tumor necrosis factor are being studies because of their ability to stimulate collagenase.
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PMID:The physiology of cervical ripening and cervical dilatation and the effect of abortifacient drugs. 222 99

To clarify the role of leukocytes effused into uterine cervix at term pregnancy, the effect of conditioned medium (MCM) of rabbit peritoneal macrophages on the production of specific collagenase by cervical cells was investigated, in vitro. MCM stimulated uterine cervical cells to induce a 10-fold increase in collagenase production as compared with the control. Similarly, production of gelatinolytic metalloproteinase (an endogenous procollagenase activator) increased to about 4-fold of the control cultures, whereas MCM did not affect [3H]thymidine incorporation into DNA. The enhancement of collagenase production was depressed by the treatment of cells with 10(-6) M cycloheximide. The MCM also contained lymphocyte-activating activity (interleukin-1). These data suggest that rabbit uterine cervical cells are able to produce both specific collagenase and gelatinolytic metalloproteinase in response to interleukin-1, and that leukocytes effused into the cervix may participate in the ripening and dilation of uterine cervix at term pregnancy.
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PMID:The role of leukocyte factors on uterine cervical ripening and dilation. 282 21

Influence of human recombinant interleukin-1 (hrIL-1) on collagen metabolism was investigated with rabbit uterine cervical fibroblasts. Enzyme-linked immunosorbent assays for collagenase and tissue inhibitor of metalloproteinases (TIMP) indicated that hrIL-1 participates in both stimulation of procollagenase production and suppression of TIMP synthesis by uterine cervical cells. IL-1 did not modulate collagen synthesis. In addition, the sensitivity to IL-1 of uterine cervix from ovariectomized rabbits was augmented by estradiol-17 beta treatment. Thus it is proposed that IL-1 accelerates collagenolysis in the cervical tissue and its effect on uterine cervix is hormonally regulated.
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PMID:Human recombinant interleukin-1 alpha-mediated stimulation of procollagenase production and suppression of biosynthesis of tissue inhibitor of metalloproteinases in rabbit uterine cervical fibroblasts. 283 71

In order to elucidate the effects of dehydroepiandrosterone sulfate (DHAS) on softening and dilatation of the uterine cervix, changes of oestriol, 17 beta-oestradiol and progesterone levels in serum and cervix, Bishop score and collagenase activity in the cervical tissue were assessed in pregnant women before and after treatment with DHAS. 17 beta-oestradiol level in the serum and cervical tissue markedly increased after the administration of DHAS, while oestriol level remained unchanged. Serum progesterone level did not change in the majority of cases, while it decreased within several hours in patients in whom delivery was accomplished within 24 hours after the administration of DHAS. Among the factors connected with the Bishop score, effacement and consistency of the cervix were remarkably improved by DHAS administration. Total collagenase activity in the cervical tissue of patients treated with DHAS was elevated by an average of 152%. These results suggest that DHAS is potent in ripening the uterine cervix through an activation of collagenase activity induced by the enhanced conversion to 17 beta-oestradiol. Thus, DHAS administration in the late stage of pregnancy is valuable in prepartal treatment for induction of labour.
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PMID:Effect of dehydroepiandrosterone sulfate on uterine cervical ripening in late pregnancy. 299 Jan 60

Factors influencing pathogenicity of various microbes found in the female lower genital tract remain incompletely understood. Protease production by cervico/vaginal microorganisms may alter or inactivate a variety of proteins important in host defense and structural-functional integrity including collagen-containing chorioamniotic membranes and uterine cervix. Host tissues may be made more susceptible to other organisms' virulence factors by protease-producing members of genital tract local flora. Microorganisms themselves may also be influenced by the presence of other microbial protease. Nonspecific protease, gelatinase, collagenase, and elastase production was examined for in vitro with use of aerobic (30) and anaerobic (25) strains of microorganisms typical of those isolated from the lower genital tract of women with premature rupture of membranes, chorioamnionitis, and puerperal infection. Microorganisms including Bacteroides bivius, Bacteroides melaninogenicus, Bacteroides fragilis, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Proteus species, and Propionibacterium acnes produce various proteases. Protease production by both acknowledged pathogenic and commensal bacteria may contribute to the occurrence of reproductive tract morbidity including premature rupture of membranes and preterm labor.
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PMID:Protease production by microorganisms associated with reproductive tract infection. 300 13


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