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Cited by 632

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1.

Open access
Hayes, C L, Spink, D C, Spink, B C, Cao, J Q, Walker, N J, Sutter, T R·1996·Proceedings of the National Academy of Sciences

Abstract

The 4-hydroxy metabolite of 17 beta-estradiol (E2) has been implicated in the carcinogenicity of this hormone. Previous studies showed that aryl hydrocarbon-receptor agonists induced a cytochrome P450 that catalyzed the 4-hydroxylation of E2. This activity was associated with human P450 1B1. To determine the relationship of the human P450 1B1 gene product and E2 4-hydroxylation, the protein was expressed in Saccharomyces cerevisiae. Microsomes from the transformed yeast catalyzed the 4- and 2-hydroxylation of E2 with Km values of 0.71 and 0.78 microM and turnover numbers of 1.39 and 0.27 nmol product min-1.nmol P450-1, respectively. Treatment of MCF-7 human breast cancer cells with the aryl hydrocarbon-receptor ligand indolo[3,2-b]carbazole resulted in a concentration-dependent increase in P450 1B1 and P450 1A1 mRNA levels, and caused increased rates of 2-, 4-, 6 alpha-, and 15 alpha-hydroxylation of E2. At an E2 concentration of 10 nM, the increased rates of 2- and 4-hydroxylation were approximately equal, emphasizing the significance of the low Km P450 1B1-component of E2 metabolism. These studies demonstrate that human P450 1B1 is a catalytically efficient E2 4-hydroxylase that is likely to participate in endocrine regulation and the toxicity of estrogens.

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Metadata

Authors
Hayes, C. L., Spink, D. C., Spink, B. C., Cao, J. Q., Walker, N. J., & Sutter, T. R.
Venue
Proceedings of the National Academy of Sciences
Published
1996-09-03
Volume
93
Issue
18
Pages
9776-9781
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2052528439
Cited by
632
References
44
FWCI
19.11
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. https://app.cochat.ai/papers/10.1073/pnas.93.18.9776
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Hayes, C. L., Spink, D. C., Spink, B. C., Cao, J. Q., Walker, N. J., & Sutter, T. R. (1996). 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.93.18.9776

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