Oestradiol inhibits collagen breakdown in the involuting rat uterus

Ryan, Janet N.; Woessner, Jeff

doi:10.1042/bj1270705

Cited by 50 publications

(17 citation statements)

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“…The effects of estrogen on uterine collagen metabolism have been studied. Ryan & Woessner (1972) showed that administration of E 2 to parturient rats strongly inhibits the loss of collagen from the involuting uterus, and found that this effect is due to inhibition of collagen degradation rather than stimulation of collagen synthesis. Furthermore, Woessner (1979) found that injection with E 2 causes a decrease in uterine collagenase activity that is correlated with the rate of collagen breakdown.…”

Section: Discussionmentioning

confidence: 99%

The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats

Tamada¹,

Shimizu²,

Inaba³

et al. 2004

Journal of Endocrinology

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It is well known that progesterone and estrogen are essential hormones for maintaining pregnancy in most mammals. Some specific roles of progesterone for the maintenance of pregnancy have been clarified, but the role of estrogen is not well known. This study examines the effects of the aromatase inhibitor, fadrozole hydrochloride (Fad), on fetuses, uterine physical properties and the mRNA expression of the uterine enzymes that are related to collagen metabolism during late pregnancy in rats. Continuous s.c. infusion with 300 µg/day Fad from day 14 of pregnancy (day 1=the day of sperm detection) reduced the concentration of plasma estradiol-17 (E 2 ), and did not change that of plasma progesterone, compared with controls. The treatment increased the intrauterine pressure and reduced the size and compliance of the uterine tissue framework. It also caused injuries (hematomata on the extremities) in about one-quarter of fetuses by day 20. The collagen content of the uterine ampullae was not changed by the treatment. Uterine mRNA expressions of matrix metalloproteinase-1 (MMP-1), which degrades collagens, and of lysyl oxidase (LO), which is necessary for the formation of intra-and inter-molecular cross-links of collagen, were examined by quantitative RT-PCR. The treatment with Fad had no effect on the expression of MMP-1 mRNA and increased that of LO mRNA. Daily s.c. injection with 0·2 µg E 2 restored the changes in uterine physical properties and the mRNA expression of LO caused by the Fad treatment, and prevented fetal injury, indicating that the influences of Fad treatment are due to estrogen deficiency but not to toxicological effects of Fad. These results imply that estrogen deficiency during late pregnancy in rats obstructs development of the uterine tissue framework so as to cause fetal injury. It is possible that an increase in the uterine expression of LO gene may be involved in this obstruction.

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Section: Discussionmentioning

confidence: 99%

The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats

Tamada¹,

Shimizu²,

Inaba³

et al. 2004

Journal of Endocrinology

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“…In the procedure of McCroskery et al (1975), al-CB7 linked to agarose was used as a ligand and was shown to have greater specificity for collagenase than did collagen, which also bound other proteins. This technique exploits a property of coUagenases which is of considerable importance in devising a means of extracting coUagenases from tissues and in evaluating the tissue levels of active enzymes, i.e., the tendency of the enzyme to bind rather tightly to collagen fibrils (Ryan and Woessner, 1971;Pardo and Pérez-Tamayo, 1975;Weeks et al, 1976). Binding of collagenase to extracellular collagen Ohlsson and Olsson (1973) and Lazarus (1973).…”

Section: Purification and Propertiesmentioning

confidence: 98%

“…As a result, collagenase-produced collagen fragments would be expected to lose the protection afforded by the triple-helical conformation of the native molecule and thereby become susceptible to a variety of extracellular proteases. A number of neutral proteases such as those in skin (Lazarus and Barrett, 1974), rheumatoid synovial tissue Steven et al, 1975), uterus (Ryan and Woessner, 1972), and tadpole skin (Harper and Gross, 1970) are capable of degrading gelatin to lower molecular weight fragments. Some neutral proteases such as the synovial fluid enzyme described by Steven et al (1975) and neutrophil elastase and cathepsin B (Starkey et al, 1977) may assist collagenases by cleaving collagen fibrils in telopeptide regions that are normally involved in the formation of intermolecular cross-links (see Section VI).…”

Section: Additional Enzymatic Degradationmentioning

confidence: 99%

The Chemistry and Biology of Collagen

Börnstein¹,

Traub²

1979

The Proteins

183

119

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“…The liver enzyme was shown to be distinct from the other known cathepsins. Recent studies on uterine involution have shown that oestradiol, which inhibits collagenolysis in vivo, has no effect on the breakdown of collagen in witro [8].The present investigation has been undertaken to compare the effect of involution on the level of collagenolytic activity with the change in acid proteinase activity. A study with activators and inhibitors was made to distinguish the separate identities of these two enzyme activities.…”

mentioning

confidence: 99%

Collagenolytic‐Cathepsin and Acid‐Proteinase Activities in the Rat Uterus during post partum Involution

Etherington¹

1973

European Journal of Biochemistry

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The digestion rates for haemoglobin and native, insoluble collagen were determined at pH 3.5 in extracts of uteri collected from rats a t 1 to 12-days post-partum. Both activities became concentrated during the early stages of involution, but the average total collagenolytic activity for the whole uteri was sharply reduced after the second day. Haemoglobin digestion (mainly cathepsin D) was most concentrated on days 3-5 and the total activity then slowly declined during the remainder of the 12-day period. Collagenolytic activity was strongly affected by thiol activators and inhibitors whereas these had little effect upon haemoglobin digestion.It is concluded that cathepsin D has no action on native insoluble collagen during involution. shown to become strongly concentrated during the early post-partum period whereas the non-lysosomal enzymes were not so retained [6].An investigation of a number of different rat tissues revealed the existence of a collagenolytic cathepsin. It degraded insoluble collagen by cleavage of the cross-linking, telopeptide region and showed optimal activity a t pH 3.5 [7]. The liver enzyme was shown to be distinct from the other known cathepsins. Recent studies on uterine involution have shown that oestradiol, which inhibits collagenolysis in vivo, has no effect on the breakdown of collagen in witro [8].The present investigation has been undertaken to compare the effect of involution on the level of collagenolytic activity with the change in acid proteinase activity. A study with activators and inhibitors was made to distinguish the separate identities of these two enzyme activities. MATERIALS AND METHODSPost-partum uteri were obtained from Wistar rats which had produced first litters a t about four months of age. Six uteri were collected for each 24 h period up to 12 days post-partum. Non-gravid uteri were obtained from virgin rats of the same age. The uteri were opened, cleaned in cold iso-osmotic saline, blotted and weighed. Extracts (loo/,, w/v) were prepared in 0.1 M sodium acetate buffer pH 5.0 containing 0.10/, (v/v) Triton X-100. This extraction procedure, which was used previously in an investigation of other rat tissues 171, ensured complete disruption of the lysosomal particles.The methods for the determination of acid proteinase and collagenolytic activities have been described in detail elsewhere [7]. The incubation time in the acid proteinase assay was 1 h and the enzyme solutions were diluted at least ten-fold. For the determination of collagenolytic activity, undiluted extract was incubated for either 6 or 16 h such that the quantity of substrate collagen solubilized did not exceed 25O/,. The rate for collagenolysis was linear with the concentration of enzyme up to ilo/o of substrate solubilized and higher values were adjusted from a correction curve.A bulked extract prepared from uteri taken a t 2-days post-parturn was used for the construction of a pH-activity curve. 0.1 M sodium formate buffers containing 5 mM cysteine were used throughout. The inhibitors p-chloromerc...

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Oestradiol inhibits collagen breakdown in the involuting rat uterus

Cited by 50 publications

References 35 publications

The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats

The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats

The Chemistry and Biology of Collagen

Collagenolytic‐Cathepsin and Acid‐Proteinase Activities in the Rat Uterus during post partum Involution

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