Differential Response to Estriol and Estradiol in the Mouse Uterus: Correlation to an Additional Nuclear Event

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Abstract
We have recently demonstrated that a single injection of potent estrogenic compounds, such as 17β-estradiol or diethylstilbestrol, results in two increases in nuclear estrogen receptor in the ovariectomized or immature mouse uterus. These nuclear increases occur 1–2 and 7–8 h post injection. In this study, we have determined whether the weak estrogen estriol could produce both nuclear events and, if so, whether both events were necessary for a complete uterine response in the mouse. Estriol injection of 10 or 33 μg/kg indicated similar nuclear receptor translocation at 1 h, with levels returning near control by 4–5 h. Injections of 166 μg/kg estriol or 10 μg/kg estradiol produced similar patterns of nuclear receptor with comparable increases occurring at ∼1 and 7–8 h. A single 10 μg/kg injection of estradiol resulted in a biphasic increase in uterine wet weight. The first increase was at ∼4 h, with the second occurring at ∼9 h and staying elevated above control values for up to 48 h. Estriol, on the other hand, given as a single injection of 20 μg/ kg, did not produce the biphasic response. When 66 μg/kg were given, the pattern qualitatively resembled the estradiol curve. Uterine glucose oxidation profiles were determined after an injection of 10 μg/kg estradiol; a significant increase in glucose-6-phosphate dehydrogenase and glucose oxidation activity in vivo was not observed until 9–12 h after injection and remained elevated for over 24 h. Similar estriol injections could not elicit the same response. Mouse uterine RNA polymerase patterns showed that both estradiol and estriol could produce initial (2 h) and late (8–10 h) increases in enzyme activity. At comparable doses, estradiol was shown to maintain an elevated enzyme activity for up to 24 h, while the pattern with estriol declined to near-control levels by 15 h. The early uterotropic responses are found with both hormones and are related to the initial receptor translocation at 1–2 h. Estradiol can elicit the second nuclear receptor increase and produce the late uterotropic responses (i.e. sustained polymerase activity,-stimulation of glucose oxidation, and a second increase in uterine wet weight) that occur by 9–12 h. Estriol does not produce this second nuclear increase nor does it produce any of the late uterotropic responses unless given in large doses. This may suggest that in the mouse uterus an additional increase in nuclear receptor is necessary for the full uterine growth response. (Endocrinology106: 1900, 1980).