View source for Steroid 11β-hydroxylase

{{Short description|Protein found in mammals}}
{{Use dmy dates|date=December 2023}}
{{Distinguish|11β-Hydroxysteroid dehydrogenase}}
{{Infobox gene}}
{{cs1 config|name-list-style=vanc}}
{{Infobox enzyme
| Name       = steroid 11β-monooxygenase
| EC_number  = 1.14.15.4
| CAS_number = 9029-66-7
| GO_code    = 0004507
| image      =
| width      =
| caption    =
}}'''Steroid 11β-hydroxylase''', also known as '''steroid 11β-monooxygenase''', is a [[steroid hydroxylase]] found in the [[zona glomerulosa]] and [[zona fasciculata]] of the [[adrenal cortex]]. Named officially the '''cytochrome P450 11B1, mitochondrial''', it is a [[protein]] that in humans is encoded by the ''CYP11B1'' [[gene]].<ref name="pmid1303253">{{cite journal | vauthors = Lifton RP, Dluhy RG, Powers M, Rich GM, Gutkin M, Fallo F, Gill JR, Feld L, Ganguly A, Laidlaw JC | display-authors = 6 | title = Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase | journal = Nature Genetics | volume = 2 | issue = 1 | pages = 66–74 | date = September 1992 | pmid = 1303253 | doi = 10.1038/ng0992-66 | hdl = 11577/133580 | s2cid = 975796 | hdl-access = free }}</ref><ref name="entrez">{{NCBI RefSeq|title = Entrez Gene: CYP11B1 cytochrome P450, family 11, subfamily B, polypeptide 1|url = https://www.ncbi.nlm.nih.gov/gene/1584| access-date = 30 November 2020 | publisher = National Center for Biotechnology Information | quote = This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane and is involved in the conversion of progesterone to cortisol in the adrenal cortex. Mutations in this gene cause congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Transcript variants encoding different isoforms have been noted for this gene.}}{{PD-notice}}</ref> The enzyme is involved in the biosynthesis of [[Adrenal gland|adrenal]] [[corticosteroids]]<ref name="pmid18215163">{{cite journal | vauthors = Zöllner A, Kagawa N, Waterman MR, Nonaka Y, Takio K, Shiro Y, Hannemann F, Bernhardt R | display-authors = 6 | title = Purification and functional characterization of human 11beta hydroxylase expressed in Escherichia coli | journal = The FEBS Journal | volume = 275 | issue = 4 | pages = 799–810 | date = February 2008 | pmid = 18215163 | doi = 10.1111/j.1742-4658.2008.06253.x | s2cid = 45997341 | doi-access =  }}</ref> by catalyzing the addition of [[hydroxyl group]]s during oxidation reactions.
==Gene==
The ''CYP11B1'' gene encodes 11β-hydroxylase, a member of the [[cytochrome P450]] superfamily of [[enzyme]]s. The cytochrome P450 proteins are [[monooxygenase]]s that catalyze many reactions involved in drug metabolism and synthesis of [[cholesterol]], [[steroid]]s and other [[lipid]]s. The product of this CYP11B1 gene is the 11β-hydroxylase protein. This protein localizes to the mitochondrial inner membrane and is involved in the conversion of various steroids in the adrenal cortex. Transcript variants encoding different isoforms have been noted for this [[gene]].<ref name="entrez" />
The ''CYP11B1'' gene is reversibly inhibited by [[etomidate]]<ref name="pmid6096625">{{cite journal |vauthors=Dörr HG, Kuhnle U, Holthausen H, Bidlingmaier F, Knorr D | title = Etomidate: a selective adrenocortical 11 beta-hydroxylase inhibitor | journal = Klinische Wochenschrift | volume = 62 | issue = 21 | pages = 1011–3 |date=November 1984 | pmid = 6096625 | doi = 10.1007/bf01711722| s2cid = 20077711 }}</ref><ref name="Lake2004">{{cite book | vauthors = Lake CL | title = Pediatric Cardiac Anesthesia | url = https://books.google.com/books?id=ymuHmUWuUsAC&pg=PA68 | access-date = 30 April 2012 | date = 7 December 2004 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-5175-9 | page = 68}}</ref> and [[metyrapone]].
==Function==
11β-hydroxylase is a [[steroidogenic enzyme]], i.e. the enzyme involved in the [[metabolism]] of [[steroid]]s. The enzyme is primarily localized in the zona glomerulosa and zona fasciculata of the adrenal cortex. The enzyme functions by introducing a hydroxyl group at carbon position 11β on the steroid nucleus, thereby facilitating the conversion of certain steroids.
Humans have two [[isozyme]]s with 11β-hydroxylase activity: CYP11B1 and CYP11B2.
CYP11B1 (11β-hydroxylase) is expressed at high levels and is regulated by [[ACTH]], while CYP11B2 ([[aldosterone synthase]]) is usually expressed at low levels and is regulated by [[angiotensin II]]. In addition to the 11β-hydroxylase activity, both isozymes have 18-hydroxylase activity.<ref name="pmid7988480">{{cite journal | vauthors = White PC, Curnow KM, Pascoe L | title = Disorders of steroid 11 beta-hydroxylase isozymes | journal = Endocrine Reviews | volume = 15 | issue = 4 | pages = 421–38 | date = August 1994 | pmid = 7988480 | doi = 10.1210/edrv-15-4-421 }}</ref> The CYP11B1 isozyme has strong 11β-hydroxylase activity, but the activity of 18-hydroxylase is only one-tenth of CYP11B2.<ref name="s2cid81304246">{{cite book | doi=10.1007/978-3-642-77763-9_41 |chapter=Steroid 11β-Hydroxylase Isozymes (CYP11B1 and CYP11B2) |s2cid=81304246 |vauthors=White PC, Curnow KM, Pascoe L|title=Cytochrome P450 |series=Handbook of Experimental Pharmacology|date=1993 |volume=105|pages=641–650|publisher=Springer |isbn=978-3-642-77765-3 }}</ref> The weak 18-hydroxylase activity of CYP11B1 explains why an adrenal with suppressed CYP11B2 expression continues to synthesize [[18-Hydroxycorticosterone|18-hydroxycorticosterone]].<ref name="pmid22145132"/>
Here are some of the steroids, grouped by catalytic activity of the CYP11B1 isozyme:
* strong activity:<ref name="pmid23322723"/><ref name="pmid29277707"/>
** [[11-deoxycortisol]] to [[cortisol]],<ref name="pmid22145132"/><ref name="pmid15761543">{{cite journal | vauthors = Mello, Penachioni, Amaral, Castro | title = 11beta-hydroxylase deficiency | language = pt | journal = Arquivos Brasileiros de Endocrinologia e Metabologia | volume = 48 | issue = 5 | pages = 713–23 | date = October 2004 | pmid = 15761543 | doi = 10.1590/s0004-27302004000500018| doi-access = free }}</ref>
** [[11-deoxycorticosterone]] to [[corticosterone]];<ref name="pmid22145132"/><ref name="pmid27928728">{{cite journal | vauthors = Bulsari K, Falhammar H | title = Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency | journal = Endocrine | volume = 55 | issue = 1 | pages = 19–36 | date = January 2017 | pmid = 27928728 | doi = 10.1007/s12020-016-1189-x | s2cid = 11153844 }}</ref>
* medium activity:<ref name="pmid23322723"/><ref name="pmid29277707"/>
** [[progesterone]] to [[11β-hydroxyprogesterone]],<ref name="pmid29277707">{{cite journal | vauthors = van Rooyen D, Gent R, Barnard L, Swart AC | title = The in vitro metabolism of 11β-hydroxyprogesterone and 11-ketoprogesterone to 11-ketodihydrotestosterone in the backdoor pathway | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 178 | pages = 203–212 | date = April 2018 | pmid = 29277707 | doi = 10.1016/j.jsbmb.2017.12.014 | s2cid = 3700135 }}</ref><ref name="pmid25850025">{{cite journal | vauthors = Turcu AF, Rege J, Chomic R, Liu J, Nishimoto HK, Else T, Moraitis AG, Palapattu GS, Rainey WE, Auchus RJ | display-authors = 6 | title = Profiles of 21-Carbon Steroids in 21-hydroxylase Deficiency | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 100 | issue = 6 | pages = 2283–90 | date = June 2015 | pmid = 25850025 | pmc = 4454804 | doi = 10.1210/jc.2015-1023 }}</ref><ref name=wj>{{cite journal |doi=10.15347/WJM/2023.003 |doi-access=free |title=Alternative androgen pathways |date=3 April 2023 |vauthors=Masiutin MM, Yadav MK |journal=WikiJournal of Medicine |volume=10 |pages=29 |s2cid=257943362 |url=https://upload.wikimedia.org/wikiversity/en/a/a7/Alternative_androgens_pathways.pdf |access-date=10 April 2024 |archive-date=24 October 2023 |archive-url=https://web.archive.org/web/20231024051038/https://upload.wikimedia.org/wikiversity/en/a/a7/Alternative_androgens_pathways.pdf |url-status=live }}{{Creative Commons text attribution notice|cc=by4|from this source=yes}}</ref>
** [[17α-Hydroxyprogesterone|17α-hydroxyprogesterone]] to [[21-deoxycortisol]],<ref name="pmid25850025"/>
** [[androstenedione]] to [[11β-Hydroxyandrostenedione|11β-hydroxyandrostenedione]];<ref name="pmid24165582">{{cite journal | vauthors = Bloem LM, Storbeck KH, Schloms L, Swart AC | title = 11β-hydroxyandrostenedione returns to the steroid arena: biosynthesis, metabolism and function | journal = Molecules | volume = 18 | issue = 11 | pages = 13228–44 | date = October 2013 | pmid = 24165582 | pmc = 6270415 | doi = 10.3390/molecules181113228 | publisher = MDPI AG | doi-access = free }}</ref>
** [[testosterone]] to [[11β-Hydroxytestosterone|11β-hydroxytestosterone]],<ref name="pmid31900912">{{cite book | vauthors = Storbeck KH, Mostaghel EA | title = Prostate Cancer | chapter = Canonical and Noncanonical Androgen Metabolism and Activity | series = Advances in Experimental Medicine and Biology | volume = 1210 | pages = 239–277 | date = 2019 | publisher = Springer | pmid = 31900912 | doi = 10.1007/978-3-030-32656-2_11 | isbn = 978-3-030-32655-5 | s2cid = 209748543 | quote = CYP11B1 and 2 have also been shown to 11β-hydroxylate T, yielding 11β-hydroxytestosterone (11OHT), though the levels produced by the adrenal are low due to the limited availability of adrenal derived T}}</ref><ref name="pmid33094617">{{cite journal | vauthors = Stárka L, Dušková M, Vítků J | title = 11-Keto-testosterone and other androgens of adrenal origin | journal = Physiological Research | volume = 69 | issue = Suppl 2 | pages = S187–S192 | date = September 2020 | pmid = 33094617 | doi = 10.33549/physiolres.934516| pmc = 8603739 | doi-access = free }}</ref><ref name="pmid29277707"/>
* weak activity:<ref name="pmid23322723"/><ref name="pmid29277707"/>
** [[corticosterone]] to [[18-Hydroxycorticosterone|18-hydroxycorticosterone]],<ref name="pmid22145132">{{cite journal | vauthors = Gupta V | title = Mineralocorticoid hypertension | journal = Indian Journal of Endocrinology and Metabolism | volume = 15 Suppl 4 | issue = 8| pages = S298–312 | date = October 2011 | pmid = 22145132 | pmc = 3230101 | doi = 10.4103/2230-8210.86972 | doi-access = free }}</ref><ref name="pmid15356073">{{cite journal | vauthors = Freel EM, Shakerdi LA, Friel EC, Wallace AM, Davies E, Fraser R, Connell JM | title = Studies on the origin of circulating 18-hydroxycortisol and 18-oxocortisol in normal human subjects | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 89 | issue = 9 | pages = 4628–33 | date = September 2004 | pmid = 15356073 | pmc = 1283128 | doi = 10.1210/jc.2004-0379}}</ref>
** [[cortisol]] to [[18-Hydroxycortisol|18-hydroxycortisol]].<ref name="pmid23322723"/><ref name="pmid15356073"/><ref name="pmid15062555">{{cite journal | vauthors = Nicod J, Dick B, Frey FJ, Ferrari P | title = Mutation analysis of CYP11B1 and CYP11B2 in patients with increased 18-hydroxycortisol production | journal = Molecular and Cellular Endocrinology | volume = 214 | issue = 1–2 | pages = 167–74 | date = February 2004 | pmid = 15062555 | doi = 10.1016/j.mce.2003.10.056 | s2cid = 617448 }}</ref><ref name="pmid28904009">{{cite journal | vauthors = Lenders JW, Williams TA, Reincke M, Gomez-Sanchez CE | title = DIAGNOSIS OF ENDOCRINE DISEASE: 18-Oxocortisol and 18-hydroxycortisol: is there clinical utility of these steroids? | journal = European Journal of Endocrinology | volume = 178 | issue = 1 | pages = R1–R9 | date = January 2018 | pmid = 28904009 | pmc = 5705277 | doi = 10.1530/EJE-17-0563 }}</ref>
==Cortisol and corticosterone metabolism==
11β-hydroxylase has strong<ref name="pmid23322723">{{cite journal | vauthors = Strushkevich N, Gilep AA, Shen L, Arrowsmith CH, Edwards AM, Usanov SA, Park HW | title = Structural insights into aldosterone synthase substrate specificity and targeted inhibition | journal = Molecular Endocrinology | volume = 27 | issue = 2 | pages = 315–24 | date = February 2013 | pmid = 23322723 | pmc = 5417327 | doi = 10.1210/me.2012-1287 }}</ref> catalytic activity during conversion of [[11-deoxycortisol]] to [[cortisol]]  and [[11-deoxycorticosterone]] to [[corticosterone]], by catalyzing the hydroxylation of carbon hydrogen bond at 11-beta position. Note the extra "–OH" added at the 11 position (near the center, on ring "C"):
<gallery>
File:Cortodoxone.svg|[[11-Deoxycortisol]]
File:Cortisol2.svg|[[Cortisol]]
</gallery>
<gallery>
File:11-Deoxycorticosterone.svg|[[11-Deoxycorticosterone]]
File:Corticosterone-2D-skeletal.svg|[[Corticosterone]]
</gallery>
==Mechanism of action==
As a mitochondrial P450 system, P450c11 is dependent on two electron transfer proteins, adrenodoxin reductase and adrenodoxin that transfer 2 electrons from NADPH to the P450 for each monooxygenase reaction catalyzed by the enzyme. In most respects this process of electron transfer appears similar to that of [[P450scc]] system that catalyzes cholesterol side chain cleavage.<ref name="pmid6783659">{{cite journal | vauthors = Hanukoglu I, Privalle CT, Jefcoate CR | title = Mechanisms of ionic activation of adrenal mitochondrial cytochromes P-450scc and P-45011 beta | journal = J. Biol. Chem. | volume = 256 | issue = 9 | pages = 4329–35 | date = May 1981 | doi = 10.1016/S0021-9258(19)69437-8 | pmid = 6783659 | url = http://www.jbc.org/content/256/9/4329.full.pdf | doi-access = free | access-date = 21 July 2012 | archive-date = 16 September 2012 | archive-url = https://web.archive.org/web/20120916170821/http://www.jbc.org/content/256/9/4329.full.pdf | url-status = live }}</ref> Similar to P450scc the process of electrons transfer is leaky leading to superoxide production. The rate of electron leakage during metabolism depends on the functional groups of the steroid substrate.<ref name="pmid7893157">{{cite journal | vauthors = Rapoport R, Sklan D, Hanukoglu I | title = Electron leakage from the adrenal cortex mitochondrial P450scc and P450c11 systems: NADPH and steroid dependence | journal = Arch. Biochem. Biophys. | volume = 317 | issue = 2 | pages = 412–6 | date = March 1995 | pmid = 7893157 | doi = 10.1006/abbi.1995.1182 | url = https://zenodo.org/record/890751 | access-date = 26 June 2019 | archive-date = 20 May 2020 | archive-url = https://web.archive.org/web/20200520080418/https://zenodo.org/record/890751 | url-status = live }}</ref>
==Regulation==
The expression of the enzyme in adrenocortical cells is regulated by the trophic hormone corticotropin ([[ACTH]]).<ref name="pmid2173715">{{cite journal | vauthors = Hanukoglu I, Feuchtwanger R, Hanukoglu A | title = Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells | journal = J. Biol. Chem. | volume = 265 | issue = 33 | pages = 20602–8 | date = November 1990 | doi = 10.1016/S0021-9258(17)30545-8 | pmid = 2173715 | url = http://www.jbc.org/content/265/33/20602.full.pdf | doi-access = free | access-date = 21 July 2012 | archive-date = 16 September 2012 | archive-url = https://web.archive.org/web/20120916170728/http://www.jbc.org/content/265/33/20602.full.pdf | url-status = live }}</ref>
==Clinical significance==
A mutation in genes encoding 11β-hydroxylase is associated with [[congenital adrenal hyperplasia due to 11β-hydroxylase deficiency]].
11β-hydroxylase is involved in the metabolism of [[17α-Hydroxyprogesterone|17α-hydroxyprogesterone]] to [[21-deoxycortisol]],<ref name="pmid25850025"/> in cases of [[congenital adrenal hyperplasia due to 21-hydroxylase deficiency]].<ref name="pmid31450227">{{cite journal | vauthors = Miller WL | title = Congenital Adrenal Hyperplasia: Time to Replace 17OHP with 21-Deoxycortisol | journal = Hormone Research in Paediatrics | volume = 91 | issue = 6 | pages = 416–420 | year = 2019 | pmid = 31450227 | doi = 10.1159/000501396 | s2cid = 201733086 | doi-access = free }}</ref><ref name="pmid37873849">{{cite journal |vauthors=Greaves RF, Kumar M, Mawad N, Francescon A, Le C, O'Connell M, Chi J, Pitt J |title=Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation |journal=Int J Neonatal Screen |volume=9 |issue=4 |date=October 2023 |page=58 |pmid=37873849 |pmc=10594498 |doi=10.3390/ijns9040058 |url= |doi-access=free }}</ref>
==See also==
* [[Steroidogenic enzyme]]
==Additional images==
[[File:Steroidogenesis.svg|thumb|center|500px|[[Steroidogenesis]], showing steroid 11-beta-hydroxylase vertically at right.]]
<gallery>
File:Corticosteroid-biosynthetic-pathway-rat.png|Corticosteroid biosynthetic pathway in rat
File:Trimethyl_steroid-nomenclature.png|Steroid numbering
</gallery>
==References==
{{reflist}}
==Further reading==
{{refbegin|32em}}
* {{cite journal | vauthors = Helmberg A | title = Twin genes and endocrine disease: CYP21 and CYP11B genes | journal = Acta Endocrinol. | volume = 129 | issue = 2 | pages = 97–108 |date=August 1993 | pmid = 8372604 | doi = 10.1530/acta.0.1290097}}
* {{cite journal |vauthors=Stowasser M, Gunasekera TG, Gordon RD | title = Familial varieties of primary aldosteronism | journal = Clin. Exp. Pharmacol. Physiol. | volume = 28 | issue = 12 | pages = 1087–90 |date=December 2001 | pmid = 11903322 | doi = 10.1046/j.1440-1681.2001.03574.x | s2cid = 23091842 }}
* {{cite journal |vauthors=Helmberg A, Ausserer B, Kofler R | title = Frame shift by insertion of 2 basepairs in codon 394 of CYP11B1 causes congenital adrenal hyperplasia due to steroid 11 beta-hydroxylase deficiency | journal = J. Clin. Endocrinol. Metab. | volume = 75 | issue = 5 | pages = 1278–81 |date=November 1992 | doi = 10.1210/jcem.75.5.1430088 | pmid = 1430088 }}
* {{cite journal |vauthors=Pascoe L, Curnow KM, Slutsker L, Connell JM, Speiser PW, New MI, White PC | title = Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 89 | issue = 17 | pages = 8327–31 |date=September 1992 | pmid = 1518866 | pmc = 49911 | doi = 10.1073/pnas.89.17.8327 | bibcode = 1992PNAS...89.8327P | doi-access = free }}
* {{cite journal |vauthors=Kawamoto T, Mitsuuchi Y, Toda K, Yokoyama Y, Miyahara K, Miura S, Ohnishi T, Ichikawa Y, Nakao K, Imura H | title = Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 89 | issue = 4 | pages = 1458–62 |date=February 1992 | pmid = 1741400 | pmc = 48470 | doi = 10.1073/pnas.89.4.1458 | bibcode = 1992PNAS...89.1458K | doi-access = free }}
* {{cite journal |vauthors=White PC, Dupont J, New MI, Leiberman E, Hochberg Z, Rösler A | title = A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin | journal = J. Clin. Invest. | volume = 87 | issue = 5 | pages = 1664–7 |date=May 1991 | pmid = 2022736 | pmc = 295260 | doi = 10.1172/JCI115182 }}
* {{cite journal |vauthors=Kawamoto T, Mitsuuchi Y, Toda K, Miyahara K, Yokoyama Y, Nakao K, Hosoda K, Yamamoto Y, Imura H, Shizuta Y | title = Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta | journal = FEBS Lett. | volume = 269 | issue = 2 | pages = 345–9 |date=September 1990 | pmid = 2401360 | doi = 10.1016/0014-5793(90)81190-Y  | s2cid = 35151332 | doi-access =  }}
* {{cite journal |vauthors=Mornet E, Dupont J, Vitek A, White PC | title = Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta) | journal = J. Biol. Chem. | volume = 264 | issue = 35 | pages = 20961–7 |date=December 1989 | doi = 10.1016/S0021-9258(19)30030-4 | pmid = 2592361 | doi-access = free }}
* {{cite journal |vauthors=Chua SC, Szabo P, Vitek A, Grzeschik KH, John M, White PC | title = Cloning of cDNA encoding steroid 11 beta-hydroxylase (P450c11) | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 84 | issue = 20 | pages = 7193–7 |date=October 1987 | pmid = 3499608 | pmc = 299256 | doi = 10.1073/pnas.84.20.7193 | bibcode = 1987PNAS...84.7193C | doi-access = free }}
* {{cite journal |vauthors=Naiki Y, Kawamoto T, Mitsuuchi Y, Miyahara K, Toda K, Orii T, Imura H, Shizuta Y | title = A nonsense mutation (TGG [Trp116]-->TAG [Stop]) in CYP11B1 causes steroid 11 beta-hydroxylase deficiency | journal = J. Clin. Endocrinol. Metab. | volume = 77 | issue = 6 | pages = 1677–82 |date=December 1993 | doi = 10.1210/jcem.77.6.7903314 | pmid = 7903314 }}
* {{cite journal |vauthors=Joehrer K, Geley S, Strasser-Wozak EM, Azziz R, Wollmann HA, Schmitt K, Kofler R, White PC | title = CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency | journal = Hum. Mol. Genet. | volume = 6 | issue = 11 | pages = 1829–34 |date=October 1997 | pmid = 9302260 | doi = 10.1093/hmg/6.11.1829 | doi-access = free }}
* {{cite journal |vauthors=Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES | title = Characterization of single-nucleotide polymorphisms in coding regions of human genes | journal = Nat. Genet. | volume = 22 | issue = 3 | pages = 231–8 |date=July 1999 | pmid = 10391209 | doi = 10.1038/10290 | s2cid = 195213008 }}
* {{cite journal |vauthors=Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A | title = Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis | journal = Nat. Genet. | volume = 22 | issue = 3 | pages = 239–47 |date=July 1999 | pmid = 10391210 | doi = 10.1038/10297 | s2cid = 4636523 }}
* {{cite journal |vauthors=Cao PR, Bernhardt R | title = Interaction of CYP11B1 (cytochrome P-45011 beta) with CYP11A1 (cytochrome P-450scc) in COS-1 cells | journal = Eur. J. Biochem. | volume = 262 | issue = 3 | pages = 720–6 |date=June 1999 | pmid = 10411633 | doi = 10.1046/j.1432-1327.1999.00414.x | doi-access = free }}
* {{cite journal |vauthors=Loidi L, Quinteiro C, Barros F, Domínguez F, Barreiro J, Pombo M | title = The C494F variant in the CYP11B1 gene is a sequence polymorphism in the Spanish population | journal = J. Clin. Endocrinol. Metab. | volume = 84 | issue = 12 | pages = 4749 |date=December 1999 | pmid = 10599751 | doi = 10.1210/jcem.84.12.6272-6 | doi-access = free }}
* {{cite journal |vauthors=Chabre O, Portrat-Doyen S, Chaffanjon P, Vivier J, Liakos P, Labat-Moleur F, Chambaz E, Morel Y, Defaye G | title = Bilateral laparoscopic adrenalectomy for congenital adrenal hyperplasia with severe hypertension, resulting from two novel mutations in splice donor sites of CYP11B1 | journal = J. Clin. Endocrinol. Metab. | volume = 85 | issue = 11 | pages = 4060–8 |date=November 2000 | pmid = 11095433 | doi = 10.1210/jcem.85.11.6897 | doi-access = free }}
* {{cite journal |vauthors=Fisher A, Friel EC, Bernhardt R, Gomez-Sanchez C, Connell JM, Fraser R, Davies E | title = Effects of 18-hydroxylated steroids on corticosteroid production by human aldosterone synthase and 11beta-hydroxylase | journal = J. Clin. Endocrinol. Metab. | volume = 86 | issue = 9 | pages = 4326–9 |date=September 2001 | doi = 10.1210/jcem.86.9.7797 | pmid = 11549669 | doi-access = free }}
* {{cite journal |vauthors=Hampf M, Dao NT, Hoan NT, Bernhardt R | title = Unequal crossing-over between aldosterone synthase and 11beta-hydroxylase genes causes congenital adrenal hyperplasia | journal = J. Clin. Endocrinol. Metab. | volume = 86 | issue = 9 | pages = 4445–52 |date=September 2001 | doi = 10.1210/jcem.86.9.7820 | pmid = 11549691 | doi-access = free }}
{{refend}}
==External links==
* {{MeshName|Steroid+11-beta-hydroxylase}}
{{Oxygenases}}
{{Steroid hydroxylases}}
{{Cytochrome P450}}
{{Mitochondrial enzymes}}
[[Category:Enzymes]]
[[Category:Metabolism]]
[[Category:Steroid hormone biosynthesis]]