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Hormonal regulation of collagenolysis in uterine cervical fibroblasts. Modulation of synthesis of procollagenase, prostromelysin and tissue inhibitor of metalloproteinases (TIMP) by progesterone and oestradiol-17 beta.

ABSTRACT: Rabbit uterine cervical fibroblasts produced a large amount of matrix metalloproteinases (MMPs) such as collagenase (MMP-1) and stromelysin (MMP-3) and a small relatively amount of tissue inhibitor of metalloproteinases (TIMP). When cells were treated with progesterone or oestradiol-17 beta, both steroids concurrently decreased the level of procollagenase and prostromelysin in the culture media and the steady-state levels of the respective mRNAs. On the other hand, the level of TIMP in the culture media and the steady-state level of its mRNA were simultaneously increased by these steroids. Similarly, the suppression of production of MMPs and the augmentation of TIMP production by both steroids were observed with interleukin 1 (IL-1)-treated cells, but the action of progesterone was more effective than that of oestradiol-17 beta in the IL-1-untreated and -treated cells. These results suggest that collagenolysis in uterine cervical fibroblasts is negatively regulated by steroid hormones via the acceleration of TIMP production and the suppression of synthesis of MMPs at the pretranslational level.

SUBMITTER: Sato T

PROVIDER: S-EPMC1150103 | biostudies-other | 1991 May

REPOSITORIES: biostudies-other

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Procollagenase activator produced by rabbit uterine cervical fibroblasts.

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Project description:1. A method is described for separating uterine epithelium that is 80% pure and connective-tissue stroma that is 60% pure. This was used to study the effects of steroid hormones on total and nuclear-protein synthesis in these tissues. 2. Oestradiol-17beta given alone produces mitoses in the epithelium but not in the stroma. It stimulated incorporation in vitro of [(14)C]lysine into total protein, histones and acidic nuclear proteins to a greater extent in epithelium than stroma. Incorporation into acidic nuclear proteins was most markedly stimulated, reaching four to six times the normal value 4h after treatment, and then declining rapidly. This peak was only seen in epithelial preparations. 3. After pretreatment with progesterone, oestradiol-17beta has the reverse effect, producing mitoses only in stroma. Progesterone alone had no effect on the amounts or rates of incorporation of [(14)C]lysine into stromal nuclear proteins, but changes after oestradiol-17beta treatment were similar to those seen in epithelium with oestradiol-17beta alone. In the epithelium, progesterone alone depressed incorporation into histones and acidic nuclear proteins, but did not abolish the subsequent response to oestradiol-17beta. With this treatment there was a rapid, large and transient increase in incorporation into epithelial total protein not seen with oestradiol-17beta alone. 4. Progesterone had no qualitative effect on the distribution of specific oestrogen-binding proteins, as judged by sucrose-density-gradient centrifugation. However, progesterone treatment increased the uptake in vivo of [6,7-(3)H]oestradiol-17beta by stroma, and it is possible that this is important although the differences were not apparent after labelling in vitro.

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Characterization of uterine heterogeneous nuclear ribonucleic acid and the effect of oestradiol-17 beta on its synthesis.

Project description:An early response to the administration of oestradiol-17 beta to immature rats is a dramatic stimulation in the synthesis of uterine hnRNA (heterogenous nuclear RNA). High-molecular-weight fractions of the hnRNA were purified and subfractionated on poly(U)-Sepharose into fractions that differed in their poly(A) content and their size profile on polyacrylamide gels. Oestrogen treatment of the rats stimulated the synthesis of all three fractions of high-molecular-weight hnRNA, but the kinetics of synthesis, degree of stimulation and size distribution of the newly synthesize RNA differed in each fraction.

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