steroid 17alpha-hydroxylase

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/10/12 21:21:29」(JST)

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Cytochrome P450 17A1, also called steroid 17-alpha-monooxygenase, 17α-hydroxylase, 17,20 lyase, or 17,20 desmolase, is an enzyme of the hydroxylase type that in humans is encoded by the CYP17A1 gene on chromosome 10.^[4] It is ubiquitously expressed in many tissues and cell types, including the zona reticularis of the adrenal cortex and zona fasciculata as well as gonadal tissues.^[5]^[6] This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are generally regarded as monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids, including the remarkable carbon-carbon bond scission catalyzed by this enzyme. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities, and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. More specifically, CYP17A1 acts upon pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 of the steroid D ring (the hydroxylase activity), or acts upon 17-hydroxyprogesterone and 17-hydroxypregnenolone to split the side-chain off the steroid nucleus (the lyase activity).^[6] The CYP17A1 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.^[7]

Structure

Gene

The CYP17A1 gene resides on chromosome 10 at the band 10q24.3 and contains 8 exons.^[4] The cDNA of this gene spans a length of 1527 bp.^[8]

Protein

CYP17A1 is a 57.4 kDa protein that belongs to the cytochrome P450 family.^[9]^[10] The protein encoded by its cDNA is composed of 508 amino acid residues. As an enzyme, CYP17A1 possesses an active site that associates with a heme prosthetic group to catalyze biosynthetic reactions.^[8] Based on its known structures while bound to two steroidal inhibitors, abiraterone and TOK-001, CYP17A1 possesses the canonical cytochrome P450 fold present in other complex P450 enzymes that participate in steroidogenesis or cholesterol metabolism, though it orients the steroid ligands toward the F and G helices, perpendicular to the heme group, rather than the β1 sheet.^[11]^[12]

Function

CYP17A1 is a member of the cytochrome P450 superfamily of enzymes localized in the endoplasmic reticulum. Proteins in this family are monooxygenases that catalyze synthesis of cholesterol, steroids and other lipids and are involved in drug metabolism.^[4] CYP17A1 has both 17a-hydroxylase activity and 17,20-lyase activity. The 17a-hydroxylase activity of CYP17A1 is required for the generation of glucocorticoids such as cortisol, but both the hydroxylase and 17,20-lyase activities of CYP17A1 are required for the production of androgenic and oestrogenic sex steroids by converting 17α-hydroxypregnenolone (17OHPreg) to dehydroepiandrosterone (DHEA).^[13] Mutations in this gene are associated with isolated steroid-17 alpha-hydroxylase deficiency, 17-alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia.^[14]

Furthermore, the 17,20-lyase activity is dependent on cytochrome P450 oxidoreductase (POR) cytochrome b5 (CYB5) and phosphorylation.^[15]^[16]^[17] Cytochrome b5 acts as a facilitator for 17,20 lyase activity of CYP17A1 and can donate second electron to some P450s. In humans the production of testosterone via pregnenolone to17-OHPreg and DHEA by the CYP17A1 requires POR.^[18] Human P450c17 is phosphorylated on serine and threonine residues by a cAMP-dependent protein kinase. Phosphorylation of P450c17 increases 17,20-lyase activity, while dephosphorylation virtually eliminates this activity.^[19]

Clinical significance

Mutations in this gene are associated with rare forms of congenital adrenal hyperplasia, specifically 17 alpha-hydroxylase deficiency/17,20-lyase deficiency and isolated 17,20-lyase deficiency.^[20]

In humans, the CYP17A1 gene is largely associated with endocrine effects and steroid hormone metabolism.^[21]^[22]^[23] Furthermore, mutations in the CYP17A1 gene are associated with rare forms of congenital adrenal hyperplasia, in particular 17 alpha-hydroxylase deficiency/17,20-lyase deficiency and isolated 17,20-lyase deficiency.^[24] Overall, CYP17A1 is an important target for inhibition in the treatment of prostate cancer because it produces androgen that is required for tumor cell growth.^[25] Currently, the FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold that is similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1.^[25] Potent inhibitors of the CYP17A1 enzyme provide a last line defense against ectopic androgenesis in advanced prostate cancer.^[26]

Clinical marker

A multi-locus genetic risk score study based on a combination of 27 loci, including the CYP17A1 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).^[27]

As a drug target

CYP17 inhibitors

The drug abiraterone, which is used to treat castration-resistant prostate cancer, blocks the biosynthesis of androgens by inhibiting the CYP17A1 enzyme. Abiraterone binds in the active site of the enzyme and coordinates the heme iron through its pyridine nitrogen, mimicking the subtrate.^[28]

Since 2014, galeterone has been in phase III clinical trials for castration-resistant prostate cancer.^[29]

Steroidogenesis

17α-hydroxylase converts pregnenolone and progesterone to their 17-hydroxy forms, and converts 17-hydroxypregnenolone and 17-hydroxyprogesterone to DHEA and androstenedione, respectively. It corresponds to the downward arrows in this reaction scheme.

Steroidogenesis, showing, at left side, both reactions of 17-alpha hydroxylase, and both actions of 17, 20 lyase.

Additional images

Pregnenolone
17-Hydroxypregnenolone
Progesterone
17-Hydroxyprogesterone
Steroid numbering

References

^ "Drugs that physically interact with Steroid 17-alpha-hydroxylase/17,20 lyase view/edit references on wikidata".
^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ ^a ^b ^c "CYP17A1 cytochrome P450 family 17 subfamily A member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-09-27.
^ "BioGPS - your Gene Portal System". biogps.org. Retrieved 2016-10-11.
^ ^a ^b Boulpaep EL; Boron, WF (2005). Medical physiology: a cellular and molecular approach. St. Louis, Mo: Elsevier Saunders. p. 1180. ISBN 1-4160-2328-3.
^ Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS (June 2015). "Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials". Lancet. 385 (9984): 2264–71. doi:10.1016/S0140-6736(14)61730-X. PMID 25748612.
^ ^a ^b Vasaitis TS, Bruno RD, Njar VC (May 2011). "CYP17 inhibitors for prostate cancer therapy". The Journal of Steroid Biochemistry and Molecular Biology. 125 (1-2): 23–31. doi:10.1016/j.jsbmb.2010.11.005. PMID 21092758.
^ "CYP17A1 - Steroid 17-alpha-hydroxylase/17,20 lyase - Homo sapiens (Human) - CYP17A1 gene & protein". www.uniprot.org. Retrieved 2016-10-11.
^ Estrada DF, Laurence JS, Scott EE (February 2016). "Cytochrome P450 17A1 Interactions with the FMN Domain of Its Reductase as Characterized by NMR". The Journal of Biological Chemistry. 291 (8): 3990–4003. doi:10.1074/jbc.M115.677294. PMID 26719338.
^ DeVore NM, Scott EE (February 2012). "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001". Nature. 482 (7383): 116–9. doi:10.1038/nature10743. PMID 22266943.
^ Petrunak EM, DeVore NM, Porubsky PR, Scott EE (November 2014). "Structures of human steroidogenic cytochrome P450 17A1 with substrates". The Journal of Biological Chemistry. 289 (47): 32952–64. doi:10.1074/jbc.M114.610998. PMID 25301938.
^ DeVore NM, Scott EE (February 2012). "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001". Nature. 482 (7383): 116–9. doi:10.1038/nature10743. PMC 3271139. PMID 22266943.
^ "CYP17A1 cytochrome P450 family 17 subfamily A member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-09-27.
^ Udhane SS, Dick B, Hu Q, Hartmann RW, Pandey AV (September 2016). "Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis". Biochemical and Biophysical Research Communications. 477 (4): 1005–10. doi:10.1016/j.bbrc.2016.07.019. PMID 27395338.
^ Pandey AV, Miller WL (April 2005). "Regulation of 17,20 lyase activity by cytochrome b5 and by serine phosphorylation of P450c17". The Journal of Biological Chemistry. 280 (14): 13265–71. doi:10.1074/jbc.M414673200. PMID 15687493.
^ Zhang LH, Rodriguez H, Ohno S, Miller WL (November 1995). "Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome". Proceedings of the National Academy of Sciences of the United States of America. 92 (23): 10619–23. PMC 40663. PMID 7479852.
^ Fukami M, Homma K, Hasegawa T, Ogata T (April 2013). "Backdoor pathway for dihydrotestosterone biosynthesis: implications for normal and abnormal human sex development". Developmental Dynamics. 242 (4): 320–9. doi:10.1002/dvdy.23892. PMID 23073980.
^ Zhang LH, Rodriguez H, Ohno S, Miller WL (November 1995). "Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome". Proceedings of the National Academy of Sciences of the United States of America. 92 (23): 10619–23. PMC 40663. PMID 7479852.
^ "Entrez Gene: CYP17A1 cytochrome P450, family 17, subfamily A, polypeptide 1".
^ Ma YN, Cao CY, Wang QW, Gui WJ, Zhu GN (October 2016). "Effects of azocyclotin on gene transcription and steroid metabolome of hypothalamic-pituitary-gonad axis, and their consequences on reproduction in zebrafish (Danio rerio)". Aquatic Toxicology. 179: 55–64. doi:10.1016/j.aquatox.2016.08.006. PMID 27571716.
^ Legendre A, Elie C, Ramambason C, Manens L, Souidi M, Froment P, Tack K (August 2016). "Endocrine effects of lifelong exposure to low-dose depleted uranium on testicular functions in adult rat". Toxicology. 368-369: 58–68. doi:10.1016/j.tox.2016.08.014. PMID 27544493.
^ Yadav R, Petrunak EM, Estrada DF, Scott EE (August 2016). "Structural insights into the function of steroidogenic cytochrome P450 17A1". Molecular and Cellular Endocrinology. doi:10.1016/j.mce.2016.08.035. PMID 27566228.
^ Kostin VA, Zolottsev VA, Kuzikov AV, Masamrekh RA, Shumyantseva VV, Veselovsky AV, Stulov SV, Novikov RA, Timofeev VP, Misharin AY (November 2016). "Oxazolinyl derivatives of [17(20)E]-21-norpregnene differing in the structure of A and B rings. Facile synthesis and inhibition of CYP17A1 catalytic activity". Steroids. 115: 114–122. doi:10.1016/j.steroids.2016.06.002. PMID 27505042.
^ ^a ^b Bonomo S, Hansen CH, Petrunak EM, Scott EE, Styrishave B, Jørgensen FS, Olsen L (2016-01-01). "Promising Tools in Prostate Cancer Research: Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors". Scientific Reports. 6: 29468. doi:10.1038/srep29468. PMID 27406023.
^ Bordeau BM, Ciulla DA, Callahan BP (September 2016). "Hedgehog Proteins Consume Steroidal CYP17A1 Antagonists: Potential Therapeutic Significance in Advanced Prostate Cancer". ChemMedChem. 11 (18): 1983–6. doi:10.1002/cmdc.201600238. PMID 27435344.
^ Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS (June 2015). "Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials". Lancet. 385 (9984): 2264–71. doi:10.1016/S0140-6736(14)61730-X. PMID 25748612.
^ PDB: 3ruk; DeVore NM, Scott EE (February 2012). "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001". Nature. 482 (7383): 116–9. doi:10.1038/nature10743. PMC 3271139. PMID 22266943.
^ "Tokai Pharmaceuticals' Reformulated Galeterone Demonstrates Robust PSA Reductions in Advanced Prostate Cancer Patients" (Press release). Tokai Pharmaceuticals. January 29, 2014.

External links

CYP17A1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 多嚢胞性卵巣症候群におけるステロイドホルモン代謝 steroid hormone metabolism in polycystic ovary syndrome
2. 自己免疫性副腎不全の病因 pathogenesis of autoimmune adrenal insufficiency
3. 思春期における多嚢胞性卵巣症候群の病態生理および病因 pathophysiology and etiology of polycystic ovary syndrome in adolescents
4. 副腎アンドロゲンの測定 measurement of adrenal androgens
5. 女性化乳房の疫学、病態生理、および原因 epidemiology pathophysiology and causes of gynecomastia

English Journal

CYP21A2 expression is localized in the developing distal epithelium of the human perinatal lung and is compatible with in situ production and intracrine actions of active glucocorticoids.

Bouhaddioui W1, Provost PR2, Tremblay Y3.
The Journal of steroid biochemistry and molecular biology.J Steroid Biochem Mol Biol.2016 Oct;163:12-9. doi: 10.1016/j.jsbmb.2016.03.024. Epub 2016 Mar 19.
Glucocorticoids play essential roles in lung development. We investigated for expression of CYP21A2 (21-hydroxylase) as well as for the presence of the corresponding protein and identification of CYP21A2-expressing cells in several human developing lungs. Expression of some related genes was also as
PMID 27004467

Hedgehog Proteins Consume Steroidal CYP17A1 Antagonists: Potential Therapeutic Significance in Advanced Prostate Cancer.

Bordeau BM1, Ciulla DA1, Callahan BP2.
ChemMedChem.ChemMedChem.2016 Sep 20;11(18):1983-6. doi: 10.1002/cmdc.201600238. Epub 2016 Jul 20.
Abiraterone, a potent inhibitor of the human enzyme CYP17A1 (cytochrome P450c17), provides a last line of defense against ectopic androgenesis in advanced prostate cancer. Herein we report an unprecedented off-target interaction between abiraterone and oncogenic hedgehog proteins. Our experiments in
PMID 27435344

Di-(2-ethylhexyl) phthalate inhibits testosterone level through disturbed hypothalamic-pituitary-testis axis and ERK-mediated 5α-Reductase 2.

Ha M1, Guan X2, Wei L2, Li P3, Yang M2, Liu C4.
The Science of the total environment.Sci Total Environ.2016 Sep 1;563-564:566-75. doi: 10.1016/j.scitotenv.2016.04.145. Epub 2016 May 4.
Di-(2-ethylhexyl) phthalate (DEHP) has reproductive toxicity and can affect male reproductive development. In order to clarify adverse effects of DEHP on testicular physiology and testosterone production, Sprague-Dawley (SD) rats were dosed daily with DEHP by gavage for 30days; TM3 cells (mouse Leyd
PMID 27155079

Japanese Journal

Adult granulosa cell tumors of the ovary: A retrospective study of 30 cases with respect to the expression of steroid synthesis enzymes

Journal of Gynecologic Oncology 28(4), 2017-07
NAID 120006318900

成熟雄マウスへのニッケル投与が精巣機能へおよぼす影響

日本毒性学会学術年会 43.1(0), P-174, 2016
NAID 130005260709

妊娠期に使用される解熱鎮痛薬の胎仔期投与がマウス雄性生殖機能に及ぼす影響

日本毒性学会学術年会 41.1(0), O-2, 2014
NAID 130005468529

Related Pictures

★リンクテーブル★

リンク元	「アルドステロン産生腺腫」

「アルドステロン産生腺腫」

CYP17A1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3RUK, 3SWZ, 4NKV, 4NKW, 4NKX, 4NKY, 4NKZ
Identifiers
Aliases	CYP17A1, CPT7, CYP17, P450C17, S17AH, cytochrome P450 family 17 subfamily A member 1
External IDs	OMIM: 609300 MGI: 88586 HomoloGene: 73875 GeneCards: 1586
Targeted by Drug
abiraterone
Gene ontology
Molecular function	• iron ion binding; • oxygen binding; • 17-alpha-hydroxyprogesterone aldolase activity; • metal ion binding; • steroid 17-alpha-monooxygenase activity; • monooxygenase activity; • heme binding; • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; • lyase activity; • oxidoreductase activity;
Cellular component	• cell projection; • endoplasmic reticulum membrane; • intracellular membrane-bounded organelle; • membrane; • axon; • neuronal cell body; • endoplasmic reticulum; • mitochondrion;
Biological process	• response to ionizing radiation; • response to fungicide; • response to cytokine; • phenol-containing compound metabolic process; • male gonad development; • phthalate metabolic process; • biphenyl metabolic process; • Leydig cell differentiation; • response to organic cyclic compound; • response to retinoic acid; • progesterone metabolic process; • response to steroid hormone; • adrenal gland development; • response to organic substance; • response to gonadotropin; • androgen biosynthetic process; • glucocorticoid biosynthetic process; • response to nutrient levels; • dibenzo-p-dioxin metabolic process; • response to acetate; • cellular response to antibiotic; • response to insecticide; • sterol metabolic process; • response to cAMP; • response to methylmercury; • positive regulation of steroid hormone biosynthetic process; • cellular response to lipopolysaccharide; • hippocampus development; • oxidation-reduction process; • ovulation; • response to toxic substance; • response to herbicide; • organic acid metabolic process; • response to drug; • cellular response to gonadotropin stimulus; • hormone biosynthetic process; • steroid biosynthetic process; • steroid metabolic process; • sex differentiation;
	Sources:Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	1586
	13074
	ENSG00000148795
	ENSMUSG00000003555
	P05093
	P27786
	NM_000102
	NM_007809
	NP_000093.1
	NP_031835.3
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

英: aldosterone-producing adenoma, APA, aldosterone producing adenoma
関: 原発性アルドステロン症、副腎皮質ホルモン

病理

3βHSD：陽性
P450c17：陰性

[1] "Drugs that physically interact with Steroid 17-alpha-hydroxylase/17,20 lyase view/edit references on wikidata".

[2] "Human PubMed Reference:".

[3] "Mouse PubMed Reference:".

[:0-4] "CYP17A1 cytochrome P450 family 17 subfamily A member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-09-27.

[5] "BioGPS - your Gene Portal System". biogps.org. Retrieved 2016-10-11.

[isbn1-4160-2328-3-6] Boulpaep EL; Boron, WF (2005). Medical physiology: a cellular and molecular approach. St. Louis, Mo: Elsevier Saunders. p. 1180. ISBN 1-4160-2328-3.

[7] Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS (June 2015). "Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials". Lancet. 385 (9984): 2264–71. doi:10.1016/S0140-6736(14)61730-X. PMID 25748612.

[:1-8] Vasaitis TS, Bruno RD, Njar VC (May 2011). "CYP17 inhibitors for prostate cancer therapy". The Journal of Steroid Biochemistry and Molecular Biology. 125 (1-2): 23–31. doi:10.1016/j.jsbmb.2010.11.005. PMID 21092758.

[9] "CYP17A1 - Steroid 17-alpha-hydroxylase/17,20 lyase - Homo sapiens (Human) - CYP17A1 gene & protein". www.uniprot.org. Retrieved 2016-10-11.

[10] Estrada DF, Laurence JS, Scott EE (February 2016). "Cytochrome P450 17A1 Interactions with the FMN Domain of Its Reductase as Characterized by NMR". The Journal of Biological Chemistry. 291 (8): 3990–4003. doi:10.1074/jbc.M115.677294. PMID 26719338.

[11] DeVore NM, Scott EE (February 2012). "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001". Nature. 482 (7383): 116–9. doi:10.1038/nature10743. PMID 22266943.

[12] Petrunak EM, DeVore NM, Porubsky PR, Scott EE (November 2014). "Structures of human steroidogenic cytochrome P450 17A1 with substrates". The Journal of Biological Chemistry. 289 (47): 32952–64. doi:10.1074/jbc.M114.610998. PMID 25301938.

[13] DeVore NM, Scott EE (February 2012). "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001". Nature. 482 (7383): 116–9. doi:10.1038/nature10743. PMC 3271139. PMID 22266943.

[14] "CYP17A1 cytochrome P450 family 17 subfamily A member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-09-27.

[15] Udhane SS, Dick B, Hu Q, Hartmann RW, Pandey AV (September 2016). "Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis". Biochemical and Biophysical Research Communications. 477 (4): 1005–10. doi:10.1016/j.bbrc.2016.07.019. PMID 27395338.

[16] Pandey AV, Miller WL (April 2005). "Regulation of 17,20 lyase activity by cytochrome b5 and by serine phosphorylation of P450c17". The Journal of Biological Chemistry. 280 (14): 13265–71. doi:10.1074/jbc.M414673200. PMID 15687493.

[17] Zhang LH, Rodriguez H, Ohno S, Miller WL (November 1995). "Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome". Proceedings of the National Academy of Sciences of the United States of America. 92 (23): 10619–23. PMC 40663. PMID 7479852.

[18] Fukami M, Homma K, Hasegawa T, Ogata T (April 2013). "Backdoor pathway for dihydrotestosterone biosynthesis: implications for normal and abnormal human sex development". Developmental Dynamics. 242 (4): 320–9. doi:10.1002/dvdy.23892. PMID 23073980.

[19] Zhang LH, Rodriguez H, Ohno S, Miller WL (November 1995). "Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome". Proceedings of the National Academy of Sciences of the United States of America. 92 (23): 10619–23. PMC 40663. PMID 7479852.

[20] "Entrez Gene: CYP17A1 cytochrome P450, family 17, subfamily A, polypeptide 1".

[21] Ma YN, Cao CY, Wang QW, Gui WJ, Zhu GN (October 2016). "Effects of azocyclotin on gene transcription and steroid metabolome of hypothalamic-pituitary-gonad axis, and their consequences on reproduction in zebrafish (Danio rerio)". Aquatic Toxicology. 179: 55–64. doi:10.1016/j.aquatox.2016.08.006. PMID 27571716.

[22] Legendre A, Elie C, Ramambason C, Manens L, Souidi M, Froment P, Tack K (August 2016). "Endocrine effects of lifelong exposure to low-dose depleted uranium on testicular functions in adult rat". Toxicology. 368-369: 58–68. doi:10.1016/j.tox.2016.08.014. PMID 27544493.

[23] Yadav R, Petrunak EM, Estrada DF, Scott EE (August 2016). "Structural insights into the function of steroidogenic cytochrome P450 17A1". Molecular and Cellular Endocrinology. doi:10.1016/j.mce.2016.08.035. PMID 27566228.

[24] Kostin VA, Zolottsev VA, Kuzikov AV, Masamrekh RA, Shumyantseva VV, Veselovsky AV, Stulov SV, Novikov RA, Timofeev VP, Misharin AY (November 2016). "Oxazolinyl derivatives of [17(20)E]-21-norpregnene differing in the structure of A and B rings. Facile synthesis and inhibition of CYP17A1 catalytic activity". Steroids. 115: 114–122. doi:10.1016/j.steroids.2016.06.002. PMID 27505042.

[Bonomo_2016-25] Bonomo S, Hansen CH, Petrunak EM, Scott EE, Styrishave B, Jørgensen FS, Olsen L (2016-01-01). "Promising Tools in Prostate Cancer Research: Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors". Scientific Reports. 6: 29468. doi:10.1038/srep29468. PMID 27406023.

[26] Bordeau BM, Ciulla DA, Callahan BP (September 2016). "Hedgehog Proteins Consume Steroidal CYP17A1 Antagonists: Potential Therapeutic Significance in Advanced Prostate Cancer". ChemMedChem. 11 (18): 1983–6. doi:10.1002/cmdc.201600238. PMID 27435344.

[27] Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS (June 2015). "Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials". Lancet. 385 (9984): 2264–71. doi:10.1016/S0140-6736(14)61730-X. PMID 25748612.

[pmid22266943-28] PDB: 3ruk; DeVore NM, Scott EE (February 2012). "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001". Nature. 482 (7383): 116–9. doi:10.1038/nature10743. PMC 3271139. PMID 22266943.

[Tokai2014-29] "Tokai Pharmaceuticals' Reformulated Galeterone Demonstrates Robust PSA Reductions in Advanced Prostate Cancer Patients" (Press release). Tokai Pharmaceuticals. January 29, 2014.

v t e Cytochromes, oxygenases: cytochrome P450 (EC 1.14)

CYP1	A1 A2 B1

CYP2	A6 A7 A13 B6 C8 C9 C18 C19 D6 E1 F1 J2 R1 S1 U1 W1

CYP3 (CYP3A)	A4 A5 A7 A43

CYP4	A11 A22 B1 F2 F3 F8 F11 F12 F22 V2 X1 Z1

CYP5-20	CYP5 (A1) CYP7 (A1, B1) CYP8 (A1, B1) CYP11 (A1, B1, B2) CYP17 (A1) CYP19 (A1) CYP20 (A1)

CYP21-51	CYP21 (A2) CYP24 (A1) CYP26 (A1, B1, C1) CYP27 (A1, B1, C1) CYP39 (A1) CYP46 (A1) CYP51 (A1)

v t e Steroid hormone metabolism modulators

HMGCR	Inhibitors: Atorvastatin Cerivastatin Fluvastatin Lovastatin Mevastatin Pitavastatin Pravastatin Rosuvastatin Simvastatin

FPS	Inhibitors: Alendronic acid Clodronic acid Etidronic acid Ibandronic acid Incadronic acid Pamidronic acid Risedronic acid Tiludronic acid Zoledronic acid

24-DHCR24	20,25-Diazacholesterol Clomifene Triparanol

20,22-Desmolase (P450scc)	Inhibitors: 22-ABC 3,3′-Dimethoxybenzidine 3-Methoxybenzidine Aminoglutethimide Canrenone Cyanoketone Danazol Etomidate Ketoconazole Mitotane Spironolactone Trilostane

17α-Hydroxylase, 17,20-Lyase	Inhibitors: 22-ABC 22-Oxime Δ⁴-Abiraterone Abiraterone Abiraterone acetate Amphenone Bifluranol Bifonazole Canrenone CFG-920 Clotrimazole Cyanoketone Cyproterone acetate Danazol Econazole Flutamide Galeterone Gestrinone Isoconazole Ketoconazole L-39 Levoketoconazole Liarozole LY-207,320 MDL-27,302 Miconazole Mifepristone Nilutamide Orteronel Pioglitazone Prochloraz Rosiglitazone Seviteronel Spironolactone Stanozolol SU-9055 SU-10603 TGF-β Tioconazole Troglitazone VN/87-1 YM116

3α-HSD	Inhibitors: Coumestrol Daidzein Genistein Indomethacin Medroxyprogesterone acetate Inducers: Fluoxetine Fluvoxamine Mirtazapine Paroxetine Sertraline Venlafaxine

3β-HSD	Inhibitors: 4-MA Δ⁴-Abiraterone Abiraterone Abiraterone acetate Azastene Cyanoketone Cyproterone acetate Danazol Epostane Genistein Gestrinone Medrogestone Medroxyprogesterone acetate Metyrapone Norethisterone Oxymetholone Pioglitazone Rosiglitazone Trilostane Troglitazone

11β-HSD	Inhibitors: 11α-Hydroxyprogesterone 11β-Hydroxyprogesterone 18α-Glycyrrhizic acid ABT-384 Acetoxolone Carbenoxolone Enoxolone (glycyrrhetinic acid) Epigallocatechin gallate Glycyrrhizin (glycyrrhizic acid) Progesterone

21-Hydroxylase	Inhibitors: Aminoglutethimide Amphenone B Bifonazole Canrenone Clotrimazole Diazepam Econazole Genistein Isoconazole Ketoconazole Levoketoconazole Metyrapone Miconazole Midazolam Spironolactone Tioconazole

11β-Hydroxylase	Inhibitors: Δ⁴-Abiraterone Abiraterone Abiraterone acetate Aminoglutethimide Canrenone Etomidate Fadrozole FETO Ketoconazole Levoketoconazole Metomidate Metyrapol Metyrapone Mitotane Potassium canrenoate Spironolactone Trilostane

18-Hydroxylase	Inhibitors: 18-Ethynylprogesterone (18-ethinylprogesterone) 18-Vinylprogesterone Aminoglutethimide Canrenone FAD286 Fadrozole Ketoconazole LCI699 Metyrapone Mespirenone Potassium canrenoate Spironolactone

17β-HSD	Inhibitors: Danazol Simvastatin

5α-Reductase	Inhibitors: 22-Oxime Δ⁴-Abiraterone Abiraterone Abiraterone acetate Alfatradiol Azelaic acid β-Sitosterol Bexlosteride Chlormadinone acetate Cl-4AS-1 Dutasteride Epitestosterone Epristeride Fatty acids (α-linolenic acid, linoleic acid, γ-linolenic acid, monolinolein, oleic acid) Finasteride Ganoderic acid Gestodene Izonsteride L-39 Lapisteride Oxendolone Saw palmetto TFM-4AS-1 Turosteride Vitamin B6 Zinc

Aromatase	Inhibitors: 4-AT 4-Cyclohexylaniline 4-Hydroxytestosterone 5α-DHNET 20α-Dihydroprogesterone Abyssinone II Aminoglutethimide Anastrozole Ascorbic acid (vitamin C) Atamestane ATD Bifonazole CGP-45,688 CGS-47,645 Chalconoids (e.g., isoliquiritigenin) Clotrimazole Corynesidone A Coumestrol DHT Difeconazole Econazole Ellagitannins Endosulfan Exemestane Fadrozole Fatty acids (e.g., conjugated linoleic acid, linoleic acid, linolenic acid, palmitic acid) Fenarimol Finrozole Flavonoids (e.g., 7-hydroxyflavone, 7-hydroxyflavanone, 7,8-DHF, acacetin, apigenin, baicalein, biochanin A, chrysin, EGCG, gossypetin, hesperetin, liquiritigenin, myricetin, naringenin, pinocembrin, rotenone, quercetin, sakuranetin, tectochrysin) Formestane Imazalil Isoconazole Ketoconazole Letrozole Liarozole Melatonin MEN-11066 Miconazole Minamestane Nimorazole NKS01 Norendoxifen ORG-33,201 Penconazole Phenytoin Prochloraz PGE2 (dinoprostone) Plomestane Prochloraz Propioconazole Pyridoglutethimide Quinolinoids (e.g., berberine, casimiroin, triptoquinone A, XHN22, XHN26, XHN27) Resorcylic acid lactones (e.g., zearalenone) Rogletimide Stilbenoids (e.g., resveratrol) Talarozole Terpenoids (e.g., dehydroabietic acid, (–)-dehydrololiolide, retinol (vitamin A), Δ⁹-THC, tretinoin) Testolactone Tioconazole Triadimefon Triadimenol Troglitazone Valproic acid Vorozole Xanthones (e.g., garcinone D, garcinone E, α-mangostin, γ-mangostin, monodictyochrome A, monodictyochrome B) YM-511 Zinc Inducers: Atrazine Flavonoids (e.g., genistein, quercetin)

SST/EST	4′OH-CB79 6-Hydroxyflavone 2,6-Dichloro-4-nitrophenol (DCNP) Equol Galangin Genistein Parabens (e.g., butylparaben) Pentachlorophenol (PCP) Triclosan

STS	AHBS Danazol Estrone-3-O-sulfamate (EMATE) Irosustat (STX64, 667 Coumate, BN-83495) KW-2581 Progestogens SR-16157 STX213 STX681 STX1938

27-Hydroxylase	Inhibitors: Anastrozole Bicalutamide Dexmedetomidine Fadrozole Posaconazole Ravuconazole

Others	Inhibitors: Inhibit estradiol degradation: Cimetidine

See also: Androgenics • Estrogenics • Glucocorticoidics • Mineralocorticoidics • Progestogenics

v t e Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)

1.14.11: 2-oxoglutarate	Prolyl hydroxylase Lysyl hydroxylase

1.14.13: NADH or NADPH	Flavin-containing monooxygenase FMO1 FMO2 FMO3 FMO4 FMO5 Nitric oxide synthase NOS1 NOS2 NOS3 Cholesterol 7 alpha-hydroxylase Methane monooxygenase 3A4 Lanosterol 14 alpha-demethylase 24-hydroxycholesterol 7α-hydroxylase

1.14.14: reduced flavin or flavoprotein	19A1 2D6 2E1

1.14.15: reduced iron-sulfur protein	11B1 11B2 11A1

1.14.16: reduced pteridine (BH4 dependent)	Phenylalanine hydroxylase Tyrosine hydroxylase Tryptophan hydroxylase

1.14.17: reduced ascorbate	Dopamine beta-hydroxylase

1.14.18-19: other	Tyrosinase Stearoyl-CoA desaturase-1

1.14.99 - miscellaneous	Cyclooxygenase Heme oxygenase (HMOX1) Squalene monooxygenase 17A1 21A2

v t e Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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P450c17