Intrauterine Injection of Cholera Toxin Induces Estrogen-Like Uterine Growth 1

Abstract

Uterine growth in response to estrogen involves nuclear interaction of cytoplasmic estrogen receptors. The magnitude of the uterine growth response, however, and other observations have led to the suggestion that an additional mechanism or mechanisms of estrogen action may be at work in the uterus. This was investigated indirectly by examining estrogen-like growth responses of the uterus to the intrauterine (i.u.) injection of cholera toxin and water. Ovariectomized rats received either a subcutaneous injection of estradiol or vehicle and an i.u. injection of cholera toxin, water, or nothing. At 4 h after treatment of uterine wet weight was determined, and at 24 h the uterine protein/DNA ratio, [3H] leucine incorporation into protein, and [3H] thymidine incorporation into DNA were measured. Estradiol caused a 1.5-fold increase in the protein/DNA ratio and cholera toxin caused a 2.0-fold increase. Similarly, estradiol increased uterine wet weight 2.1-fold and cholera toxin increased it 1.9-fold. Estradiol and cholera toxin caused similar increases in the incorporation of [3H]leucine into protein: 3.3-fold and 2.3-fold, respectively. The effects of the treatments on the incorporation of [3H] thymidine into DNA were even greater, with estradiol producing a 10.3-fold increase, cholera toxin a 12.0-fold increase, and water a 3.6-fold increase. Since vascular permeability is known to be increased in the uterus by estrogen and in other systems by cholera toxin, these results support the idea of a relationship between uterine growth and increased vascular permeability.