Characterization and estrogen regulation of growth factor activity from uterus

Acid-stable uterine-derived growth factor activity, extracted from uteri of several species (rat, rabbit and bovine), stimulates DNA synthesis as measured by [3H]thymidine incorporation into hamster uterine carcinosarcoma (UCS) cells. A time course of [3H]thymidine incorporation demonstrates maximum incorporation at 24 h. These extracts also stimulate [3H]thymidine incorporation in a variety of other cell types from 17 beta-estradiol (E2) target tissues and non-target tissues. Uterine extracts from E2-treated ovariectomized rats show a 3-fold increase in growth factor activity above control values. Activity is elevated within 18-24 h after estradiol injection and remains elevated wtih subsequent injections. Growth factor activity is acid-stable, heat-labile, reduced by trypsin but not reduced by treatment with dextran-coated charcoal. Gel filtration shows molecular weight (Mr) heterogeneity with activity eluting at Mr of 10,000-30,000. Since uterine extracts can restore in vitro the estrogen-regulated properties of uterine growth observed previously in vivo, it is possible that the substances found in these extracts may be mediators of E2 actions.