Hormonal control of uterine growth: Alterations in luminal epithelial deoxyribonucleic acid synthesis after intraluminal application of estrogen

Administration of a single injection of estradiol (E₂) causes a maximum increase in DNA synthesis in the uterine luminal epithelium approximately 24 h later. We previously reported that animals receiving a second injection of E₂ 15-18 h after the first show an apparent decrease in DNA synthesis measured in this cell type at 24 h. This apparent decrease in DNA synthesis is due to a shift in the time course of DNA synthesis rather than an absolute decrease in this parameter. In this report we demonstrate that this inhibitory effect of a second injection of E₂ is also observed after intraluminal instillation of the hormone. This effect is dose dependent and appears to result from a shift in the time course of luminal epithelial DNA synthesis. The intraluminal instillation of E₂ produces the same pattern of nuclear receptor localization as sc administration of the hormone. These results suggest that this inhibitory effect we previously described results primarily from a direct action of E₂ on the luminal epithelium.