Further studies on the role of estradiol in the induction of progesterone-regulated uteroglobin synthesis in the rabbit uterus

The role of a continuous presence of estradiol for the induction of uteroglobin, a progester-one-regulated protein in the rabbit uterus, was studied by administration of various doses of estradiol (0.1–2000 μg per day) along with a constant dose of progesterone (2 mg per day) for 5 days to estrous rabbits. Smaller doses of estradiol slightly potentiated the action of progester-one, as judged by measurements of luminal fluid uteroglobin content and of uteroglobin mRNA activity in the uterus. By contrast, higher doses of estradiol almost totally inhibited the action of progesterone. A 50% inhibition of uteroglobin secretion was achieved with a daily dose of 3 μg of estradiol (1.5 μg/kg per day). A similar dose of estradiol was required to decrease by 50% the progesterone-induced accumulation of uteroglobin mRNA activity. The decline in the uteroglobin content in the uterine flushes elicited by estradiol treatment was not due to inhibition of the release of this protein from the endometrial cells, since all the doses of estradiol given along with progesterone diminished uterine tissue uteroglobin content from that achieved with progesterone alone. When estradiol was administered alone to estrous rabbits, a dose-dependent increase was seen in both tissue and luminal fluid uteroglobin levels. The maximal luminal fluid uteroglobin content was about 10-fold higher than that in the control animals, but was only less than 1% of that achieved with a daily dose of 2 mg of progesterone. A half-maximal increase in the uterine fluid uteroglobin concentration was obtained with a daily dose of 3 μg (1.5 μg/kg per day) i.e. with the same dose as that required for a 50% inhibition of progesterone action.