Cited by 121Pharmacogenetics and Drug MetabolismSteroid Chemistry and BiochemistryEstrogen and related hormone effects

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

Niwa, Toshiro, Murayama, Norie, Imagawa, Yurie, Yamazaki, Hiroshi·2015·Drug Metabolism Reviews

DOI 10.3109/03602532.2015.1011658

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.3109/03602532.2015.1011658

Cites

88 of 88 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians
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
Human Cytochrome P450 Enzymes: A Status Report Summarizing Their Reactions, Substrates, Inducers, and Inhibitors
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
Characterization of the Oxidative Metabolites of 17β-Estradiol and Estrone Formed by 15 Selectively Expressed Human Cytochrome P450 Isoforms
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
Expression of Modified Human Cytochrome P450 3A4 in Escherichia coli and Purification and Reconstitution of the Enzyme
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
Progesterone and Testosterone Hydroxylation by Cytochromes P450 2C19, 2C9, and 3A4 in Human Liver Microsomes
Yamazaki, H., & Shimada, T. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.0302 · Cited by 310
Differential expression of CYP1A1 and CYP1B1 in human breast epithelial cells and breast tumor cells
Spink, D. C. (1998) · Carcinogenesis · doi:10.1093/carcin/19.2.291 · Cited by 310
Purification and characterization of human placental aromatase cytochrome P-450.
Kellis, J. T., & Vickery, L. E. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61364-x · Cited by 290
Catalytic properties of polymorphic human cytochrome P450 1B1 variants
Shimada, T. (1999) · Carcinogenesis · doi:10.1093/carcin/20.8.1607 · Cited by 272
Estrogen and its metabolites are carcinogenic agents in human breast epithelial cells
Russo, J., Lareef, M. H., Balogh, G., Guo, S., & Russo, I. H. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00390-x · Cited by 252
Drug metabolism and transport during pregnancy: how does drug disposition change during pregnancy and what are the mechanisms that cause such changes?
Isoherranen, N., & Thummel, K. E. (2013) · Drug Metabolism and Disposition · doi:10.1124/dmd.112.050245 · Cited by 239
Roles of NADPH-P450 Reductase and Apo- and Holo-Cytochrome b5 on Xenobiotic Oxidations Catalyzed by 12 Recombinant Human Cytochrome P450s Expressed in Membranes of Escherichia coli
Yamazaki, H., Nakamura, M., Komatsu, T., Ohyama, K., Hatanaka, N., Asahi, S., Shimada, N., Guengerich, F. P., Shimada, T., Nakajima, M., et al. (2002) · Protein Expression and Purification · doi:10.1006/prep.2001.1578 · Cited by 234
The role of cytochrome b5 in the biosynthesis of androgens by human P450c17
Katagiri, M., Kagawa, N., & Waterman, M. R. (1995) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1995.1173 · Cited by 223
Multiple forms of human P450 expressed in Saccharomyces cerevisiae
Imaoka, S., Yamada, T., Hiroi, T., Hayashi, K., Sakaki, T., Yabusaki, Y., & Funae, Y. (1996) · Biochemical Pharmacology · doi:10.1016/0006-2952(96)00052-4 · Cited by 207
4β‐hydroxycholesterol, an endogenous marker of CYP3A4/5 activity in humans
Diczfalusy, U., Nylén, H., Elander, P., & Bertilsson, L. (2010) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2010.03773.x · Cited by 202
Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16[alpha ]-hydroxylation of 17[beta ]-estradiol
Badawi, A. F., Cavalieri, E. L., & Rogan, E. G. (2001) · Metabolism · doi:10.1053/meta.2001.25592 · Cited by 184
Roles of Cytochromes P450 1A2 and 3A4 in the Oxidation of Estradiol and Estrone in Human Liver Microsomes
Yamazaki, H., Shaw, P. M., Guengerich, F. P., & Shimada, T. (1998) · Chemical Research in Toxicology · doi:10.1021/tx970217f · Cited by 182
The 17, 20-Lyase Activity of Cytochrome P450c17 from Human Fetal Testis Favors the Δ5Steroidogenic Pathway
Flück, C. E., Miller, W. L., & Auchus, R. J. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030143 · Cited by 173
Cytochrome P450s and cholesterol homeostasis
Pikuleva, I. A. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.05.014 · Cited by 162
Isoform-Specific Regulation of Cytochromes P450 Expression by Estradiol and Progesterone
Choi, S.-Y., Koh, K. H., & Jeong, H. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.112.046276 · Cited by 161
Multisite kinetic models for CYP3A4: simultaneous activation and inhibition of diazepam and testosterone metabolism.
Kenworthy, K. E., Clarke, S. E., Andrews, J., & Houston, J. B. (2001) · PubMed · Cited by 160
Expression and purification of functional human 17 alpha-hydroxylase/17,20-lyase (P450c17) in Escherichia coli. Use of this system for study of a novel form of combined 17 alpha-hydroxylase/17,20-lyase deficiency.
Imai, T., Globerman, H., Gertner, J. M., Kagawa, N., & Waterman, M. R. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)36570-6 · Cited by 153
Modulation of the activity of human 17 α-hydroxylase-17,20-lyase (CYP17) by cytochrome b 5: endocrinological and mechanistic implications
Lee-Robichaud, P., Wright, J. N., Akhtar, M. E., & Akhtar, M. (1995) · Biochemical Journal · doi:10.1042/bj3080901 · Cited by 145
CHOLESTEROL-METABOLIZING CYTOCHROMES P450
Pikuleva, I. A. (2006) · Drug Metabolism and Disposition · doi:10.1124/dmd.105.008789 · Cited by 133
4β‐Hydroxycholesterol as an endogenous marker for CYP3A4/5 activity. Stability and half‐life of elimination after induction with rifampicin
Diczfalusy, U., Kanebratt, K. P., Bredberg, E., Andersson, T. B., Böttiger, Y., & Bertilsson, L. (2008) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2008.03309.x · Cited by 130
Nature of cytochromes P450 involved in the 2-/4-hydroxylations of estradiol in human liver microsomes
Kerlan, V., Dréano, Y., Bercovici, J. P., Beaune, P. H., Floch, H. H., & Berthou, F. (1992) · Biochemical Pharmacology · doi:10.1016/0006-2952(92)90068-t · Cited by 129
Role of polymorphic human cytochrome P450 enzymes in estrone oxidation
Cribb, A. E., Knight, M. J., Dryer, D., Guernsey, J., Hender, K., Tesch, M., & Saleh, T. M. (2006) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-05-0801 · Cited by 118
Cholesterol 25-hydroxylation activity of CYP3A
Honda, A., Miyazaki, T., Ikegami, T., Iwamoto, J., Maeda, T., Hirayama, T. T., Saito, Y., Teramoto, T., & Matsuzaki, Y. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m014084 · Cited by 115
Heterologous Expression and Kinetic Characterization of Human Cytochromes P-450: Validation of a Pharmaceutical Tool for Drug Metabolism Research
Masimirembwa, C. M., Otter, C. A., Berg, M., Jönsson, M., Leidvik, B., Jonsson, E., Johansson, T., Bäckman, A., Edlund, A., & Andersson, T. B. (1999) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(24)15034-9 · Cited by 106
Cytochromes P450: Roles in Diseases
Pikuleva, I. A., & Waterman, M. R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.431916 · Cited by 106
Steroid Regulation of Drug-Metabolizing Cytochromes P450
Monostory, K., & Dvořák, Z. (2011) · Current Drug Metabolism · doi:10.2174/138920011795016854 · Cited by 105
Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase
Agrawal, V., Choi, J. H., Giacomini, K. M., & Miller, W. L. (2010) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32833e0cb5 · Cited by 105
Kinetic Analysis of the Three-step Steroid Aromatase Reaction of Human Cytochrome P450 19A1
Sohl, C. D., & Guengerich, F. P. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.123711 · Cited by 103
Effect of two mutations of human CYP1B1, G61E and R469W, on stability and endogenous steroid substrate metabolism
Jansson, I., Stoilov, I., Sarfarazi, M., & Schenkman, J. B. (2001) · Pharmacogenetics · doi:10.1097/00008571-200112000-00007 · Cited by 101
Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones
Niwa, T., Yabusaki, Y., Honma, K., MATSUO, N., 龍田, 佳., Ishibashi, F., & KATAGIRI, M. (1998) · Xenobiotica · doi:10.1080/004982598239290 · Cited by 97
Progesterone Oxidation by Cytochrome P450 2D Isoforms in the Brain
Hiroi, T., Kishimoto, W., Chow, T., Imaoka, S., Igarashi, T., & Funae, Y. (2001) · Endocrinology · doi:10.1210/endo.142.9.8363 · Cited by 94
Extraadrenal 21-Hydroxylation by CYP2C19 and CYP3A4: Effect on 21-Hydroxylase Deficiency
Gomes, L. G., Huang, N., Agrawal, V., Mendonça, B. B., Bachega, T. A. S. S., & Miller, W. L. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1174 · Cited by 91
Cytochrome P450 2D catalyze steroid 21-hydroxylation in the brain
Kishimoto, W., Hiroi, T., Shiraishi, M., Osada, M., Imaoka, S., Kominami, S., Igarashi, T., & Funae, Y. (2004) · Endocrinology · doi:10.1210/en.2003-1109 · Cited by 90
Recombinant CYP11B Genes Encode Enzymes that Can Catalyze Conversion of 11-Deoxycortisol to Cortisol, 18-Hydroxycortisol, and 18-Oxocortisol1
Mulatero, P., Curnow, K. M., Aupetit-Faisant, B., Foekling, M., Gomez-Sanchez, C., Veglio, F., Jeunemaitre, X., Corvol, P., & Pascoe, L. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.11.5237 · Cited by 88
Inhibition of the Human Liver Microsomal and Human Cytochrome P450 1A2 and 3A4 Metabolism of Estradiol by Deployment-Related and Other Chemicals
Usmani, K. A., Cho, T. M., Rose, R. L., & Hodgson, E. (2006) · Drug Metabolism and Disposition · doi:10.1124/dmd.106.010439 · Cited by 83
Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and Ser268 result in complete, partial, or no loss of enzymatic activity, respectively.
Wu, D. A., & Chung, B. C. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115334 · Cited by 80
Structure/Function Relationships Responsible for Coenzyme Specificity and the Isomerase Activity of Human Type 1 3β-Hydroxysteroid Dehydrogenase/Isomerase
Thomas, J. L., Duax, W. L., Addlagatta, A., Brandt, S., Fuller, R. R., & Norris, W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304752200 · Cited by 77
Comparison of Kinetic Parameters for Drug Oxidation Rates and Substrate Inhibition Potential Mediated by Cytochrome P450 3A4 and 3A5
Yamazaki, H., Niwa, T., Murayama, N., & Emoto, C. (2008) · Current Drug Metabolism · doi:10.2174/138920008783331121 · Cited by 75
Estrogen metabolism and formation of estrogen-DNA adducts in estradiol-treated MCF-10F cells
Lu, F., Zahid, M., SAEED, M. K., Cavalieri, E. L., & Rogan, E. G. (2007) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2006.12.102 · Cited by 74
Evaluation of 6β-Hydroxycortisol, 6β-Hydroxycortisone, and a Combination of the Two as Endogenous Probes for Inhibition of CYP3A4 In Vivo
Peng, C.-C., Templeton, I. E., Thummel, K. E., Davis, C. N., Kunze, K. L., & Isoherranen, N. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.53 · Cited by 73
Stereo- and regioselectivity account for the diversity of dehydroepiandrosterone (DHEA) metabolites produced by liver microsomal cytochromes P450
Miller, K. K. M., Cai, J., Ripp, S. L., Pierce, W. M., Rushmore, T. H., & Prough, R. A. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.32.3.305 · Cited by 73
Effects of Endogenous Steroids on CYP3A4-Mediated Drug Metabolism by Human Liver Microsomes
Nakamura, H., Nakasa, H., Ishii, I., Ariyoshi, N., Igarashi, T., Ohmori, S., & Kitada, M. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.5.534 · Cited by 70
CHARACTERIZATION OF TESTOSTERONE 11β-HYDROXYLATION CATALYZED BY HUMAN LIVER MICROSOMAL CYTOCHROMES P450
Choi, M. H., Skipper, P. L., Wishnok, J. S., & Tannenbaum, S. R. (2005) · Drug Metabolism and Disposition · doi:10.1124/dmd.104.003327 · Cited by 69
Induction of Hepatic CYP3A Enzymes by Pregnancy-Related Hormones: Studies in Human Hepatocytes and Hepatic Cell Lines
Papageorgiou, I. S., Grepper, S., & Unadkat, J. D. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.112.049015 · Cited by 67
Role of a disordered steroid metabolome in the elucidation of sterol and steroid biosynthesis
Shackleton, C. H. L. (2012) · Lipids · doi:10.1007/s11745-011-3605-6 · Cited by 61
Heterotropic Cooperativity in Oxidation Mediated by Cytochrome P450
Niwa, T., Murayama, N., & Yamazaki, H. (2008) · Current Drug Metabolism · doi:10.2174/138920008784746364 · Cited by 60
Defective Activity of Recombinant Cytochromes P450 3A4.2 and 3A4.16 in Oxidation of Midazolam, Nifedipine, and Testosterone
Miyazaki, M., Nakamura, K., Fujita, Y., Guengerich, F. P., Horiuchi, R., & Yamamoto, K. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.021816 · Cited by 60
Characterization of stable human aromatase expressed in E. coli
Kagawa, N., Hori, H., Waterman, M. R., & Yoshioka, S. (2004) · Steroids · doi:10.1016/j.steroids.2004.01.002 · Cited by 59
Identification of Human Hepatic Cytochrome P450 Enzymes Involved in the Biotransformation of Cholic and Chenodeoxycholic Acid
Deo, A. K., & Bandiera, S. M. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.022194 · Cited by 55
Metabolism of anabolic steroids by recombinant human cytochrome P450 enzymes
Rendić, S., Nolteernsting, E., & Schänzer, W. (1999) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(99)00400-4 · Cited by 54
Role of cytochrome P450 in estradiol metabolism in vitro.
Cheng, Z., Shu, Y., Liu, Z., Wang, L., Ouyang, D., & Zhou, H.-H. (2001) · PubMed · Cited by 54
The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver
Mäenpää, J., Pelkonen, O., Cresteil, T., & Rane, A. (1993) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(93)90152-m · Cited by 53
Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity
Schwarz, D., Kisselev, P., Schunck, W., Chernogolov, A. A., Boidol, W., Cascorbi, I., & Roots, I. (2000) · Pharmacogenetics · doi:10.1097/00008571-200008000-00005 · Cited by 53
Dehydroepiandrosterone Induces Human CYP2B6 through the Constitutive Androstane Receptor
Köhalmy, K., Tamási, V., Kob́ori, L., Sárváry, E., Pascussi, J., Porrogi, P., Rozman, D., Prough, R. A., Meyer, U., & Monostory, K. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.016303 · Cited by 53
Human cytochrome P450 3A7 has a distinct high catalytic activity for the 16alpha-hydroxylation of estrone but not 17beta-estradiol.
Lee, A. J., Conney, A. H., & Zhu, B. T. (2003) · PubMed · Cited by 49
Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6
Niwa, T., Hiroi, T., Tsuzuki, D., Yamamoto, S., Narimatsu, S., Fukuda, T., Azuma, J., & Funae, Y. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.06.030 · Cited by 45
Oxidation of Endobiotics Mediated by Xenobiotic-Metabolizing Forms of Human Cytochrome P450
Niwa, T., Murayama, N., & Yamazaki, H. (2009) · Current Drug Metabolism · doi:10.2174/138920009789895525 · Cited by 45
CYP3A4 and CYP3A7-Mediated Carbamazepine 10,11-Epoxidation Are Activated by Differential Endogenous Steroids
Nakamura, H., Torimoto, N., Ishii, I., Ariyoshi, N., Nakasa, H., Ohmori, S., & Kitada, M. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.4.432 · Cited by 44
Diversity and Substrate Specificity in the Structures of Steroidogenic Cytochrome P450 Enzymes
Sugimoto, H., & Shiro, Y. (2012) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.35.818 · Cited by 42
Effect of Psychotropic Drugs on the 21-Hydroxylation of Neurosteroids, Progesterone and Allopregnanolone, Catalyzed by Rat CYP2D4 and Human CYP2D6 in the Brain
Niwa, T., Okada, K., Hiroi, T., Imaoka, S., Narimatsu, S., & Funae, Y. (2008) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.31.348 · Cited by 40
Oxidation of Dihydrotestosterone by Human Cytochromes P450 19A1 and 3A4
Cheng, Q., Sohl, C. D., Yoshimoto, F. K., & Guengerich, F. P. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.390047 · Cited by 40
In vitroactivation of 7-benzyloxyresorufinO-debenzylation and nifedipine oxidation in human liver microsomes
Niwa, T., Shiraga, T., Yamasaki, S., Ishibashi, K., Ohno, Y., & Kagayama, A. (2003) · Xenobiotica · doi:10.1080/0049825031000121617 · Cited by 39
Inhibition of Human Cytochrome P450 3A4 by Cholesterol
Shinkyo, R., & Guengerich, F. P. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.240457 · Cited by 33
Progesterone metabolism in hepatic microsomes. Effect of the cytochrome P-450 inhibitor, ketoconazole, and the NADPH 5 alpha-reductase inhibitor, 4-MA, upon the metabolic profile in human, monkey, dog, and rat.
Swinney, D. C. (1990) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08683-0 · Cited by 31
16α-Hydroxyprogesterone: Origin, biosynthesis and receptor interaction
Storbeck, K., Swart, P., Africander, D., Conradie, R., Toit, R. L.-D., & Swart, A. C. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.11.016 · Cited by 28
Comparison of Cytochrome P450 2D6 and Variants in Terms of Drug Oxidation Rates and Substrate Inhibition
Niwa, T., Murayama, N., & Yamazaki, H. (2011) · Current Drug Metabolism · doi:10.2174/138920011795495286 · Cited by 28
Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450 reductase coexpressed in insect cells using baculovirus.
Ohmori, S., Fujiki, N., Nakasa, H., Nakamura, H., Ishii, I., Itahashi, K., & Kitada, M. (1998) · PubMed · Cited by 27
Interaction of CYP11B1 (cytochrome P‐45011β) with CYP11A1 (cytochrome P‐450scc) in COS‐1 cells
Cao, P., & Bernhardt, R. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00414.x · Cited by 26
A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio
Paracchini, V., Pedotti, P., Raimondi, S., GARTE, S. J., Bradlow, H. L., Sepkovic, D. W., & Taioli, E. (2005) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2005.119 · Cited by 25
Comparison of Cytochrome P450 2C Subfamily Members in Terms of Drug Oxidation Rates and Substrate Inhibition
Niwa, T., & Yamazaki, H. (2012) · Current Drug Metabolism · doi:10.2174/138920012802850092 · Cited by 24
Comparison of the 17α-Hydroxylase/C17,20-Lyase Activities of Porcine, Guinea Pig and Bovine P450c17 Using Purified Recombinant Fusion Proteins Containing P450c17 Linked to NADPH-P450 Reductase
Shet, M. S., Fisher, C., Tremblay, Y., Bélanger, A., Conley, A. J., Mason, J. I., & Estabrook, R. W. (2007) · Drug Metabolism Reviews · doi:10.1080/03602530701468391 · Cited by 21
Comparison of CYP3A4 and CYP3A5: The Effects of Cytochrome b5 and NADPH-cytochrome P450 Reductase on Testosterone Hydroxylation Activities
Lee, S., & Goldstein, J. A. (2012) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.dmpk-12-sh-030 · Cited by 20
Still another activity by the highly promiscuous enzyme CYP3A4: 25-hydroxylation of cholesterol
Diczfalusy, U., & Ingemar Björkhem, E. B. (2011) · Journal of Lipid Research · doi:10.1194/jlr.e017806 · Cited by 20
Comparison of Catalytic Properties of Cytochromes P450 3A4 and 3A5 by Molecular Docking Simulation
Niwa, T., Yasumura, M., Murayama, N., & Yamazaki, H. (2013) · Drug Metabolism Letters · doi:10.2174/1872312807666131229121228 · Cited by 18
Amino Acid Residues Affecting the Activities of Human Cytochrome P450 2C9 and 2C19
Niwa, T., Kageyama, A., Kishimoto, K., Yabusaki, Y., Ishibashi, F., & Katagiri, M. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.8.931 · Cited by 16
New Aspects on Primary Aldosteronism
Enberg, U., Volpe, C., & Hamberger, B. (2003) · Neurochemical Research · doi:10.1023/a:1022341619943 · Cited by 15
Comparison of the Contributions of Cytochromes P450 3A4 and 3A5 in Drug Oxidation Rates and Substrate Inhibition
Niwa, T., Murayama, N., & Yamazaki, H. (2010) · Eisei kagaku · doi:10.1248/jhs.56.239 · Cited by 12
Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population
Rais, N., Hussain, A., Chawla, Y. K., & Kohli, K. K. (2012) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2012.842 · Cited by 10
Inhibition of Human Steroidogenic Cytochrome P450 c17 by 21-Hydroxypregnenolone and Related Steroid Hormones
Niwa, T., Imamura, H., & Katagiri, M. (2012) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b12-00080 · Cited by 2

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

Sorted by citations

Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review
Schiffer, L., Barnard, L., Baranowski, E. S., Gilligan, L. C., Taylor, A. E., Arlt, W., Shackleton, C. H. L., & Storbeck, K.-H. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105439 · Cited by 450
“2, hepatic xenobiotic-metabolizing members of the CYP superfamily are able to modify steroid hormones and generate a plethora of minor steroid metabolites [116].”
Sex‐specificity in lung cancer risk
Stapelfeld, C., Dammann, C., & Maser, E. (2019) · International Journal of Cancer · doi:10.1002/ijc.32716 · Cited by 225
Intracrine androgen biosynthesis, metabolism and action revisited
Schiffer, L., Arlt, W., & Storbeck, K.-H. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.08.016 · Cited by 217
“Prostate cells also express CYP3A4 that can inactivate T by conversion to mainly 6bOH-T (with 2b-, 15a/b- and 11b-hydroxyl side product formation (Niwa et al., 2015)) and a decrease of CYP3A4 expression is observed in prostate cancer (Fujimura et al.”
Proposed Key Characteristics of Male Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Evidence in Human Health Hazard Assessments
Arzuaga, X., Smith, M. T., Gibbons, C. F., Skakkebæk, N. E., Yost, E. E., Beverly, B., Hotchkiss, A. K., Hauser, R. B., de Souza, R. P., Schrader, S. M., et al. (2019) · Environmental Health Perspectives · doi:10.1289/ehp5045 · Cited by 90
Liver and Steroid Hormones—Can a Touch of p53 Make a Difference?
Charni‐Natan, M., Aloni-Grinstein, R., Osher, E., & Rotter, V. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00374 · Cited by 91

See all 121

Authors: Niwa, T., Murayama, N., Imagawa, Y., & Yamazaki, H.
Affiliations: Shujitsu University (JP)
Showa Pharmaceutical University (JP)
Corresponding author: Yamazaki, Hiroshi
ORCID: Niwa, Toshiro
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
DOI: 10.3109/03602532.2015.1011658
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

Regioselective hydroxylation of steroid hormones by human cytochromes P450

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks