Regulation of collagenase production by steroids in uterine smooth muscle cells: An enzymatic and immunologic study
✍ Scribed by John J. Jeffrey; William T. Roswit; Lynn S. Ehlich
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 830 KB
- Volume
- 143
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
An enzyme-linked immunosorhent assay (ELISA) has been developed for rat COIL Iagenase. The assay is capable of measuring the enzyme from a variety of rat cell sources at concentrations of 10-50 ng/nil, approximately 500-1,000-fold more sensitive than radiolabelled collagen fibril assay systems. The assay is specific to collagenase from the rat: enzymes from human, tadpole, mouse, and bacterial sources failed to cross-react signiiicantly with rat enzyme. The assay is reproducible and accurate, and is capable of detecting enzyme in the presence of serum or tissue inhibitors. Using the ELISA, we have examined the eifect of a variety of hormones on the production of collagendse by rat myornetrial smooth muscle cells in culture. Of all the reproductive hormones examined, only progesterone and its synthetic derivative medroxyprogesterone acetate were capable of inhibiting the production of the enzyme by these cells. The maximally effective concentration of progesterone was 1 x 10 I'M, and that of medroxyprogesterone acetate was 1 x 10 'M. The effect of the steroid was selective: no effect on cell proliferation or on general protein synthesis was observed. In addition to the progestational steroids, the glucocorticoids were also capable of inhibiting the production of collagenase by the cells at similar nominal concentrations. However, the myornetrial cells were found actively to metabolize progesterone but not hydrocortisone in culture. Thus, the effective inhibitory concentration of progesterone was approximately ten-fold lower than that of hydrocortisone. The results of this study support the concept that progesterone plays a major role in preventing the production of collagenase in the rat uterus.