Hormonal control of uterine growth: Temporal relationships between estrogen administration and deoxyribonucleic acid synthesis

Administration of a single injection of estradiol (E₂) causes a maximum increase in DNA synthesis of all major uterine cell types approximately 24 h later. Animals given a second injection of E₂ 6–12 h after the first show an apparent increase in DNA synthesis in the luminal epithelium. Animals receiving a second injection of E₂15–18 h after the first show an apparent decrease in DNA synthesis at 24 h, which is most prominent in the luminal epithelium. This apparent decrease in DNA synthesis is most apparent if the second injection of E₂ is given 18 h after the first, and is due to a shift of 10–12 h in the time course of DNA synthesis rather than to an absolute decrease in this parameter. This shift in the time course of uterine DNA synthesis is a dose-dependent phenomenon and displays a dose-response curve similar to that for the stimulation of DNA synthesis by a single injection of E_2. A third injection of E₂ 28 h after the initial hormone treatment, again causes a shift of 10– 12 h in the time course of DNA synthesis relative to that in animals receiving two injections of hormone. These results suggest that nuclear levels of estrogen receptor, which initially increase after hormone administration, must decrease before the onset of uterine DNA synthesis.