Delayed Interactions between Progesterone and Low Doses of 17β-Estradiol in the Mouse Uterus*

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Abstract
Pregnancy is maintained in ovariectomized mice by the daily administration of 1.0 mg progesterone and a low dose of 17β-estradiol. In this study, several dose combinations of progesterone and 17β-estradiol were administered daily to nonpregnant, ovariectomized mice for periods of up to 16 days, and the occurrence of hormone interactions within the uterus, which may be relevant to the maintenance of gestation, was determined. Treatment effects on uterine weight, length, DNA, protein, RNA to DNA ratio, and the in vivo incorporation of [5-3H]uridine and L-[4,5-3H]leucine into uterine RNA and protein, respectively, were determined, as well as rates of mitosis in the luminal and glandular epithelia and stroma. When mice received 1.0 mg progesterone and 6.7–20 ng 17β-estradiol daily, a biphasic growth response occurred in the uterus. The second and larger component commenced only after the first 6 days of treatment, and was characterized by large increases in uterine length, protein, RNA to DNA ratio, and rate of uridine incorporation. There was little change in DNA, and rates of mitosis in the endometrium were generally low, but a small surge of cell division occurred in the luminal epithelium 8–12 days after the commencement of daily treatments. Such a delayed uterine response did not occur in mice receiving 1.0 mg progesterone only, 17β-estradiol only, or a combination of 1.0 mg progesterone and 60 ng 17β-estradiol. The results are discussed in relation to peripheral plasma levels of ovarian hormones in pregnant mice. It is suggested that this delayed uterine growth represents one of the mechanisms that enable the uterus to accommodate several growing conceptuses during mid pregnancy.