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Uterine estrogen sulfatase may play a more important role than the hepatic sulfatase in mediating the uterotropic action of estrone-3-sulfate

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Abstract

The estrogenic activity of sulfonated estrogens results from the release of active estrogens via desulfonation (hydrolysis) catalyzed by estrogen sulfatase. In this study, the relative importance of uterine or hepatic estrone (E1)-3-sulfatase in mediating the uterotropic action of E1-3-sulfate is evaluated by comparing its hormonal potency in animals that have comparable uterine E1-3-sulfatase activity but markedly different hepatic enzyme activity. Liver microsomes from immature or adult female Sprague-Dawley rats contained 12-or 55-fold higher E1-3-sulfatase activity, respectively, than the liver microsomes from immature or adult female CD-1 mice. In contrast, uterine whole homogenates from immature female Sprague-Dawley rats contained approx twofold higher E1-3-sulfatase activity than was detected in the uterine whole homogenates from immature female CD-1 mice. It is estimated that the total E1-3-sulfatase activity in the liver of an immature female rat or mouse is approx 1080-or 260-fold higher, respectively, than the activity in the uterus. The ED50 values for the uterotropic effect of E1-3-sulfate and E1 in immature female CD-1 mice were 240 and 8 pmol/g body wt, respectively, and the corresponding ED50 values in immature female Sprague-Dawley rats were 840 and 60 pmol/g body wt, respectively. The difference in the ratios of the uterotropic ED50 for E1-3-sulfate over that for E1 in immature rats and mice (14 and 30, respectively) is 1.14-fold, which correlates very closely with their difference in the uterine E1-3-sulfatase activity (approx twofold), but not their difference in the hepatic sulfatase activity (approx 12-fold). The results of this study provide evidence suggesting that E1-3-sulfatase in the uterus (an estrogen target organ) may play a more important role than the hepatic sulfatase in mediating the uterotropic action of sulfonated estrogens.

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Abbreviations

E1 :

estrone

E2 :

estradiol

E1-3-sulfate:

estrone-3-sulfate

E1-3-sulfatase:

estrone-3-sulfatase

ED50 :

the dose that elicits a 50% of the maximum response

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  1. Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinhuysen Road, 08854-8020, Piscataway, NJ

    Bao Ting Zhu & Jia-Huey Fu

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  1. Bao Ting Zhu
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  2. Jia-Huey Fu
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Correspondence to Bao Ting Zhu.

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Zhu, B.T., Fu, JH. Uterine estrogen sulfatase may play a more important role than the hepatic sulfatase in mediating the uterotropic action of estrone-3-sulfate. Endocr 7, 191–198 (1997). https://doi.org/10.1007/BF02778141

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  • DOI: https://doi.org/10.1007/BF02778141

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