The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index.
Regioselective hydroxylation of steroid hormones by human cytochromes P450
Abstract
This article reviews in vitro metabolic activities [including Michaelis constants (Km), maximal velocities (Vmax) and Vmax/Km] and drug-steroid interactions [such as induction and cooperativity (activation)] of cytochromes P450 (P450 or CYP) in human tissues, including liver and adrenal gland, for 14 kinds of endogenous steroid compounds, including allopregnanolone, cholesterol, cortisol, cortisone, dehydroepiandrosterone, estradiol, estrone, pregnenolone, progesterone, testosterone and bile acids (cholic acid). First, we considered the drug-metabolizing P450s. 6β-Hydroxylation of many steroids, including cortisol, cortisone, progesterone and testosterone, was catalyzed primarily by CYP3A4. CYP1A2 and CYP3A4, respectively, are likely the major hepatic enzymes responsible for 2-/4-hydroxylation and 16α-hydroxylation of estradiol and estrone, steroids that can contribute to breast cancer risk. In contrast, CYP1A1 and CYP1B1 predominantly metabolized estrone and estradiol to 2- and 4-catechol estrogens, which are endogenous ultimate carcinogens if formed in the breast. Some metabolic activities of CYP3A4, including dehydroepiandrosterone 7β-/16α-hydroxylation, estrone 2-hydroxylation and testosterone 6β-hydroxylation, were higher than those for polymorphically expressed CYP3A5. Next, we considered typical steroidogenic P450s. CYP17A1, CYP19A1 and CYP27A1 catalyzed steroid synthesis, including hydroxylation at 17α, 19 and 27 positions, respectively. However, it was difficult to predict which hepatic drug-metabolizing P450 or steroidogenic P450 will be mainly responsible for metabolizing each steroid hormone in vivo based on these results. Further research is required on the metabolism of steroid hormones by various P450s and on prediction of their relative contributions to in vivo metabolism. The findings collected here provide fundamental and useful information on the metabolism of steroid compounds.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Hepatic xenobiotic-metabolizing members of the CYP superfamily are able to modify steroid hormones and generate a plethora of minor steroid metabolites [116].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [116]
In the citing paper
“with at least 17 hepatic CYPs potentially participating in the metabolism of steroids [[116], [117], [118]].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [116]
In the citing paper
“CYP3A4 is the most abundant P450 in the liver (∼30%) (Shimada et al., 1994) and predominantly, though not exclusively, catalyses the 6β-hydroxylation of T and the 16α- and 7α-hydroxylation of DHEA (Niwa et al., 2015).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Niwa et al., 2015
In the citing paper
“Prostate cells also express CYP3A4 that can inactivate T by conversion to mainly 6βOH-T (with 2β-, 15α/β- and 11β-hydroxyl side product formation (Niwa et al., 2015))”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Niwa et al., 2015
Citations
Cites
Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., & Guengerich, F. P. (1994) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22379-5 · Cited by 2,785
Rendić, S., & Carlo, F. J. D. (1997) · Drug Metabolism Reviews · doi:10.3109/03602539709037591 · Cited by 1,165
Functional role of estrogen metabolism in target cells: review and perspectives
Zhu, B. T. (1998) · Carcinogenesis · doi:10.1093/carcin/19.1.1 · Cited by 970
Summary of information on human CYP enzymes: human P450 metabolism data
Rendić, S. (2002) · Drug Metabolism Reviews · doi:10.1081/dmr-120001392 · Cited by 819
Cytochrome b 5 Augments the 17,20-Lyase Activity of Human P450c17 without Direct Electron Transfer
Auchus, R. J., Lee, T. C., & Miller, W. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.6.3158 · Cited by 541
Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7
Williams, J. A., Ring, B. J., Cantrell, V. E., Jones, D. R., Eckstein, J., Ruterbories, K., Hamman, M. A., Hall, S. D., & Wrighton, S. A. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.8.883 · Cited by 471
Lee, A. J., Cai, M. X., Thomas, P. E., Conney, A. H., & Zhu, B. T. (2003) · Endocrinology · doi:10.1210/en.2003-0192 · Cited by 457
Developmental Expression of the Major Human Hepatic CYP3A Enzymes
Stevens, J. C., Hines, R. N., Gu, C., Koukouritaki, S. B., Manro, J. R., Tandler, P. J., & Zaya, M. J. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.054841 · Cited by 368
Gillam, E. M. J., Baba, T., Kim, B., Ohmori, S., & Guengerich, F. P. (1993) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1993.1401 · Cited by 340
Yamazaki, H., & Shimada, T. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.0302 · Cited by 310
Research works printed but not linked: 6
- Cheng Z, 2000, Acta Pharmacol Sin, 22, 148
- Kenworthy KE, 2001, Drug Metab Dispos, 29, 1644
- Lee AJ, 2003, Cancer Res, 63, 6532
- Mulatero P, 1998, J Clin Endocrinol Metab, 83, 3996
- Niwa T, 2009, Curr Drug Metab, 9, 20
- Ohmori S, 1998, Res Commun Mol Pathol Pharmacol, 100, 15
Cited by
Sorted by citations
Items 101–121 of 121
Kuno, M., Okayama, Y., Yasui, Y., Shibata, W., Moriguchi, M., Nakaya, Y., Horiuchi, M., Ido, K., Sakatoku, K., Makuuchi, Y., et al. (2025) · British Journal of Clinical Pharmacology · doi:10.1002/bcp.70264 · Cited by 1
Kandel, S. E., & Lampe, J. N. (2025) · Drug Metabolism and Disposition · doi:10.1016/j.dmd.2025.100184 · Cited by 1
Xia, X., Chen, Y., & Sun, X. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.119444 · Cited by 1
Binding Site Vectors Enable Mapping of Cytochrome P450 Functional Landscapes
Kuvek, T., Jandová, Z., Schleifer, K.-J., & Oostenbrink, C. (2026) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c02705 · Cited by 1
Nkosi, T. M., & Maseko, L. P. (2025) · Annals of Pharmacy Practice and Pharmacotherapy · doi:10.51847/dbkv1db2tx · Cited by 1
Kaya, S. I., Çetinkaya, A., & Özkan, S. A. (2026) · Discover Chemistry. · doi:10.1007/s44371-026-00621-9 · Cited by 1
Uehara, S., Higuchi, Y., Fukuda, S., Shimizu, M., Shimoi, A., Suemizu, H., & Yamazaki, H. (2026) · Drug Metabolism and Disposition · doi:10.1016/j.dmd.2026.100283 · Cited by 1
Dawood, M., Guthart, A., Ooko, E., Weiskirchen, R., Efferth, T., & Boulos, J. C. (2026) · Livers · doi:10.3390/livers6030050 · Cited by 1
Hypercortisolism: Causes, Consequences and Clinical Significance – A Review of Pathophysiology
Eldib, M., Fierro, F. E., Abad, M. O., & Correa, R. R. (2026) · Diabetes Obesity and Metabolism · doi:10.1111/dom.71022 · Cited by 1
Zakharian, E. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813814-4.00024-9 · Cited by 1
Breakdown and clearance of steroids
Honour, J. W. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-818124-9.00001-2 · Cited by 1
Polymorphism of xenobiotic biotransformation enzyme genes and their role in early pregnancy loss
Васильевич, М. С., & Shramko, S. V. (2024) · Fundamental and Clinical Medicine · doi:10.23946/2500-0764-2023-8-4-134-141 · Cited by 1
Comparison on Metabolism of Estradiol and Its 17-Sulfate by Recombinant Human CYP Isoforms
Yuasa, S., Takanashi, K., Ukiana, K., Mihara, Y., & Itoh, S. (2021) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b21-00275 · Cited by 1
Hofland, J., & de Jong, F. H. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-802175-0.00036-x
Kazakova, O. A., Alekseev, V. B., & Dolgikh, О. V. (2022) · Advances in health sciences research/Advances in Health Sciences Research · doi:10.2991/ahsr.k.220103.025
Induction of Cytochrome P450 Systems
Coleman, M. D. (2020) · doi:10.1002/9781119658016.ch4
A computational approach toward the role of biomimetic complexes in hydroxylation reactions
Monika, Yadav, O., Kumar, M., Mohapatra, R. K., Kashid, V. S., & Ansari, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-90596-1.00013-4
Zhang, Y., McDougall, C., Bar, I., & Botwright, N. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.18.670794
Metal Ions as Endocrine Disruptors
Mudashiru, B. A. (2026) · World Scientific News · doi:10.65770/oujz7977
Li, Z., Hao, Y., Yang, Y., Lei, J., Zhang, F., Song, Y., Yin, H., Dai, Z. H., Qi, S., Cao, Y., et al. (2026) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2026.117910
Metadata
- Authors
- Niwa, T., Murayama, N., Imagawa, Y., & Yamazaki, H.
- Affiliations
- Shujitsu University (JP)
- Showa Pharmaceutical University (JP)
- Corresponding author
- Yamazaki, Hiroshi
- Venue
- Drug Metabolism Reviews
- Publisher
- Informa UK Limited
- Published
- 2015-02-13
- Volume
- 47
- Issue
- 2
- Pages
- 89-110
- ISSN
- 0360-2532 (ISSN-L)
- 1097-9883
- OpenAlex
- W2041685866
- Cited by
- 121
- References
- 88
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 7 · 2023: 12 · 2022: 18 · 2021: 10 · 2020: 13 · 2019: 14 · 2018: 5 · 2017: 10 · 2016: 10 · 2015: 2
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Metabolism Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- steroid hormone metabolism, cytochrome P450, regioselective hydroxylation, CYP3A4, CYP1A2, CYP1A1, CYP1B1, CYP17A1, CYP19A1, CYP27A1, CYP3A5, enzyme induction, cooperativity, estradiol, estrone, catechol estrogens, breast cancer risk, steroidogenesis, adrenal gland, liver
- MeSH terms
- Adrenal Glands, Cholesterol, Cytochrome P-450 Enzyme System, Estradiol, Humans, Hydroxylation, Liver, Testosterone, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
