Prevention of normal mouse uterine maturation by antipain and elastatinal: suppression of peroxidase activity

We had shown previously that the serine protease inhibitors, antipain and leupeptin, restrict uterine DNA snythesis and function in adult mice. The present study is an extension, focusing on the perimaturation period. The protease inhibitors, antipain and elastatinal were tested and the end points were uterine development and peroxidase activity in the uterus. Four week old mice were treated with eigher antipain (3 mg), elastatinal (5 mg) or vehicle (control) twice daily for 3 weeks. The uteri were excised, weighed and homogenized. Subcellular fractions were prepared by differential centrifugation. Each fraction was analyzed for peroxidase activity. The weights and protein content of uteri from control mice averaged greater than twice those in either antipain or elastatinal treated mice (p less than 0.001). Peroxidase activity was sharply curtailed by both inhibitors, antipain being more active than elastatinal. Mechanistically, antipain and elastatinal may act directly on the uterus either by inhibiting key enzymes or by preventing the formation of macromolecules crucial to normal function. Alternatively, the protease inhibitors may interfere with ovarian function, thereby restricting normal uterine development.