Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

To account for reproductive failure induced by surgical deletion of paternal accessory sex glands in the golden hamster in vivo, we studied expression of vegf, FLT-1 (VEGF-R1), FLK-1 (VEGF-R2), MMP and TGF-beta in endometrium of the dam and sired embryos during 5-7 days post coitum by immunohistochemistry, in situ hybridisation, semiquantitative RT-PCR and enzyme-linked immunosorbent assay. Spatiotemporal pattern of vegf expression in the control animals was similar to that reported for intact animals by our group. Removal of paternal ampullary glands did not disturb the normal expression pattern. Removal of ventral prostate glands alone or all accessory sex glands was associated with reduction of vegf transcripts and protein levels in both the embryo and endometrium. FLT-1, FLK-1 and MMP-2 were also reduced. MMP-1 was not changed whereas TGF-beta1 expression was enhanced. There was no expression in endometrium in between implantation sites. Thus the implanted embryos had a trophic effect on growth factor production by the endometrium, and the levels of expression were determined by viability and structural integrity of the conceptus. Based on these findings we concluded that incompetent embryos sired by males without the ventral prostate gland or all accessory sex glands reduced the potential of the uterus to support pregnancy. A negative cycle of events was thus set up and eventually led to premature termination of pregnancies.
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PMID:Embryos sired by males without accessory sex glands induce failure of uterine support: a study of VEGF, MMP and TGF expression in the golden hamster. 1259 72

Opioid peptides are negative regulators of cell proliferation in several organs including the uterus. In the present study, the ontogeny of the direct inhibitory action of opioid peptides on the proliferation of cultured rat uterine cells was investigated. Uteri of 7, 14, 21, 28, 35 and 60-day-old rats were removed in a sterile way. Tissue blocks were dispersed by limited digestions with trypsin and collagenase. Cells were cultured in enriched Dulbecco's modified Eagle's medium (DMEM). Treatments were present during the entire culture period. Cell densities of the monolayers were determined by counting the cells following trypsinization and trypan blue exclusion. Rat uterine mixed cell cultures grew to confluence within 10 days. The average population doubling time gradually increased with the age of animals. Epidermal growth factor (EGF) increased cell densities of cultures from all age groups. The oestradiol (E2)-responsiveness appeared at 21 days of age. The effect of [D-Met2-Pro5]-enkephalinamide (ENK) was biphasic. ENK and [Met5]-enkephalin (OGF) decreased cell densities of both unstimulated and EGF-stimulated cultures from 7-day-old rats to the same extent. ENK failed to act in 14-day-old animals. From 21 days of age on, the E2- or EGF-stimulated proliferation was inhibited only by ENK and DAMGO, while 30 nm DPDPE, Dynorhin-A, OGF, [Leu5]-enkephalin, beta-endorphin, and morphiceptin were ineffective. The half-inhibitory concentration of ENK was 0.3 nm. The effects of ENK were prevented by concomitant treatment with naloxone. Our novel data demonstrate two different phases of the inhibitory action of opioid peptides on rat uterine cell proliferation during ontogeny with an insensitive interval in between.
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PMID:Developmental changes in the inhibition of cultured rat uterine cell proliferation by opioid peptides. 1281 31

Quantitative collagen determinations demonstrate an increase of approximately 800 per cent in the collagen content of the human uterus at term as compared with the non-pregnant state. Following parturition, there is a rapid resorption of collagen. The amount of collagen which disappears from the post partum uterus is approximately 53 gm. By the 8th day post partum, the human uterus has lost approximately 72 per cent of the total collagen which was present at term. The slopes of curves depicting alterations in collagen content of the uterus of the rat and human are virtually identical, despite the marked differences in the length of the gestational periods of the two species. The alterations in the collagen content of the human uterus during pregnancy and involution closely follow changes in total uterine weight. There is a slight decrease in per cent collagen content of the uterus during pregnancy, and an increase in the water content of the post partum uterus. Approximately 97 per cent of the collagen which is present in the human uterus at term is of the so called "insoluble" type. The physiological resorbability of uterine collagen, as evidenced by its post partum dissolution, cannot therefore be correlated with its in vitro solubility characteristics. No collagenase was demonstrable in the myometrium of post partum uteri. A 2 day post partum uterus was found to contain an enzyme which slowly degraded gelatin at pH 3.85 but was virtually inactive at pH 7,0. There is an increase in myometrial prolidase activity of approximately 75 per cent, commencing 2 days post partum. Prolidase activity remains elevated until the 8th day post partum, and subsequently falls to almost normal levels by the 5th post partum week. During the process of involution, the post partum uterus shows histological evidence of edema and partial destruction of its reticular framework.
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PMID:Alteration in the collagen content of the human uterus during pregnancy and post partum involution. 1447 28

The expression of estrogen (ER) and progesterone receptors (PR) in the endometrium is regulated by steroid hormones. An increase in plasma estrogen leads to upregulation of the number of both steroid receptors, whereas a decrease in both receptors population is due to high concentration of plasma progesterone. To study the exact effect of different concentrations of beta-estradiol and progesterone on canine epithelial and stromal endometrial cells an in vitro model from dog uterus was developed and kept for 20 days. Material was obtained from healthy dogs, undergoing ovariohysterectomy. Endometrial epithelial and stromal cells were gained after collagenase treatment, followed by filtration steps. Electron microscopy and immunolabeling were used to study cell morphology and differentiation. Immunocytochemistry was used to determine proliferation rate (Ki-67), ER and PR status on Days 3, 8, 10, 13, and 20. Mitotic activity of both cells was stimulated with different concentrations of steroids and revealed high values until cells reached confluency. ER and PR expression in confluent layer from epithelial and stromal cells was upregulated with beta-estradiol. In addition progesterone significant downregulated both receptors population in stromal cells, whereas the reduction was less pronounced in epithelial cells. Results showed that our in vitro system is a useful tool to study the influence of beta-estradiol and progesterone on cell proliferation rate, ER and PR expression. The primary cell culture model helps to avoid experiments on living animals.
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PMID:Steroid receptors in canine endometrial cells can be regulated by estrogen and progesterone under in vitro conditions. 1475 80

In women, circulating relaxin is produced by the corpus luteum of pregnancy. The levels of relaxin are predominantly determined by the luteal mass, the number of corpora lutea present. Relaxin levels are highest after ovulation induction, which stimulates formation of many corpora lutea. Elevated relaxin levels in the first trimester of pregnancy are maintained throughout pregnancy and are linearly related to preterm birth. In an in vitro model of late human pregnancy cervix, relaxin increases MMP-1 and MMP-3 and decreases TIMP-1 levels, thus acting as a positive regulator of matrix metalloproteinases. In an in vivo rhesus monkey model of early pregnancy, relaxin decreases cervical collagen content, decreases cervical lumican levels, and stimulates MMP-7 levels. Early effects of relaxin in the uterus include increasing endometrial arteriole number and increasing the number of leukocytes, uterine natural killer cells, macrophages, and neutrophils. These cells release many cytokines which contribute to changes that stimulate and facilitate uterine contractility. If these changes persist in late pregnancy, relaxin may be a mediator of labor. Excess relaxin may produce these changes at an accelerated rate, causing preterm birth.
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PMID:Mechanisms of relaxin-mediated premature birth. 1595 32

In the endotheliochorial placenta of the cat, the maternal surface epithelium and parts of the connective tissue have to be removed to bring the fetal blood vessels in close contact to the maternal capillaries. The composition of the extracellular matrix (ECM) in the feline uterus is not known and it is still not clear if and which parts of the maternal ECM persist during gestation in the placental labyrinth. We demonstrated various extracellular matrix components (collagen types I, III, IV, and laminin) and matrix metalloproteinases (MMP-1, -2, -13) using immunohistochemistry and studied the distribution of intermediate filaments (vimentin, cytokeratin) and alpha-smooth muscle actin (SMA) in the placental girdle on specimens of different stages of gestation. Collagen types I and III were mainly present in the fetal chorionic lamellae whereas diminished in the maternal placental labyrinth part. Collagen IV and laminin were expressed in fetal basement membranes and mesenchyme. Maternal endothelial cells and stromal cells showed a positive immunoreaction for anti-collagen type IV and laminin. MMP-2 was identified in the maternal stroma, including decidual cells. Endothelia of maternal blood vessels within the labyrinth contained MMP-1, -2 and -13, probably associated with angiogenesis. In the trophoblast MMP-1 and -13 were demonstrated. Maternal stem vessels were accompanied by a thick layer of syncytiotrophoblast. Around these vessels, collagen type I and SMA were present in a periendothelial region between the endothelium and the trophoblast. These findings indicate that a strictly regulated balance between ECM deposition and ECM degradation in the feline placental labyrinth is necessary for proper placental development and function.
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PMID:Extracellular matrix components and matrix degrading enzymes in the feline placenta during gestation. 1633 74

Shortened gestation is a major cause of infant mortality and morbidity. Evidence from both human and animal studies suggests that essential fatty acids of the n-6 and n-3 series play important and modifiable roles in gestational duration. We examined the influence of linolenic acid (LnA) vs. docosahexaenoic acid (DHA) on rat reproductive tissue prostaglandin (PG) and matrix metalloproteinase (MMP) indices of gestational duration. By varying the oil source of the diet, AIN-93G diets were constructed to provide either 0.7 energy % (en%) LnA, the current US intake of n-3 fatty acids, or 0.7 en% DHA. In addition, enhanced levels of 2.0 en% LnA or 2.0 e% DHA diets were also constructed. All diets contained approximately 6.0 en% linoleic acid (LA), the current US intake of LA. Four groups of 10 female rats were time-mated and fed the respective diets from conception through Day 20 of gestation. Day 20 uterus and placenta DHA were significantly increased by 160-180% by the 0.7 en% DHA diet, and by 250-350% by the 2.0 en% DHA diets in comparison to 0.7 en% LnA diet. DHA diets also significantly reduced uterus and placenta arachidonic acid content. Day 20 placenta and uterus PGE(2) and placenta PGF(2alpha) production rates were significantly reduced by 27-47% in the 0.7 en% DHA group in comparison to 0.7 en% LnA. Increasing LnA to 2.0 en% was without effect. Providing DHA at the enhanced 2.0 en% did not significantly enhance the suppression of PG production. Placenta active MMP-2 and active MMP-9 (gelatinase) production was suppressed significantly by 30-43% in the 0.7 en% DHA group in comparison to the 0.7 en% LnA group, and 2.0 en% DHA did not enhance this suppression. Placenta collagenase activity comprising the sum of MMP-1, MMP-8 and MMP-13 was also suppressed by 60% in the 0.7 en% DHA diet group with no additional effect with 2.0 en% DHA provision. These results suggest that substituting DHA for LnA even at the current US n-3 fatty acid intake of 0.7 en% is effective in suppressing indices of premature delivery and shortened gestation. Increasing LnA intake by 3-fold to 2.0 en% is not effective. The form of dietary n-3 fatty acid, DHA vs. LnA, appears to be more important than the amount.
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PMID:Dietary docosahexaenoic acid alters pregnant rat reproductive tissue prostaglandin and matrix metalloproteinase production. 1645 97

The level of cAMP in the rats uterus myocytes under the effect of active metabolites of nitrogen and oxygen (NO, NO2- and H2O2) was studied in the conditions of progesterone influence on myocytes. Suspension of cells was selected with the use of collagenase and soy-bean inhibitor of tripsine. The amount of cAMP was determined with the use of standard reagents producted by "Amersham", England. It is established that the basal level of cAMP in cells is 10.4 +/- 0.7 pmol cAMP/mg protein. Incubation of myocytes with forskoline, 0.1 mM, 10 min, resulted in its 3.4 times increase. It testifies to adenilatcyclase activity characteristic of the great majority of cell objects in the uterus myocytes. The level of cAMP in the suspension insignificantly decreases at the protracted affecting with myocytes 10 nM progesterone (1 hour). Donator of nitrogen oxide (0.1 mM sodium nitroprusside) in the presence of progesterone substantially promoted the level of cAMP in cells at the protracted action (17 +/- 3 pmol cAMP/mg protein). Nitrite-anion and hydrogen peroxide in concentration 10 nM (low physiological concentration) did not have the above effect. The results obtained prove that exactly the long-term influence of nitrogen oxide, instead of progesterone, can provide the increase of cAMP level in the uterus myometrium.
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PMID:[Active nitrogen and oxygen metabolites change cAMP level in the uterus myocytes treated by progesterone]. 1656 14

In the cow, cesarean section delivery is often followed by retention of fetal membranes. Hypothetically, the retention of fetal membranes could be prevented by intraplacental injections of the enzyme collagenase. However, the infusion of this potent proteolytic enzyme into a uterus traumatized by surgery can lead to uterine damage, including perforation. Thus, the objective of this research was to evaluate tolerance of intraplacental treatment of bacterial collagenase. A cesarean section was performed on 10 experimental cows undergoing induced delivery or diagnosed with dystocia. During the surgical procedure, 200,000 units of bacterial collagenase in 1 L of saline were infused via the umbilical arteries. A cesarean section was also performed on control cows (n = 25) affected by dystocia, but these received no collagenase. The collagenase-treated cows showed no clinical or laboratory signs of abnormality over a 3- to 4-wk observation period post treatment. When membrane retention time was set at 36 h post surgery, 20% of the experimental cows and 60% of the control cows had retained the fetal membranes. It was concluded that intraplacental administration of collagenase during cesarean section is safe. However, treatment effectiveness and economic benefits for commercial application need further study.
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PMID:Prevention of retained placenta by injection of collagenase into umbilical arteries of calves delivered by cesarean section: a tolerance study. 1672 3

Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12-24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked.
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PMID:A critical period of progesterone withdrawal precedes menstruation in macaques. 1711 70


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