Table 11.

P450 21A2

Properties	References
Physiological substrates: Progesterone, 17α-hydroxyprogesterone	(Coulter and Jaffe 1998; Zöllner et al. 2010; Parr et al. 2012; Yoshimoto et al. 2012; Pallan, Wang, et al. 2015; Pan et al. 2016; Wang et al. 2017)
Other substrate(s): Normetandienone, metandienone, 17-fluoroprogesterone
Function: Steroid 21-hydroxylase, formation of 11-deoxycorticosterone from progesterone and 11-deoxycortisol from 17α-hydroxyprogesterone (Figs. 2, 13)
Inhibition: May lead to congenital adrenal hyperplasia
Inhibitors:
Drugs:
Abiraterone a (Malikova et al. 2017)
Imidazole drugs b (e.g. clotrimazole, bifonazole, isoconazole, miconazole, ketoconazole, tioconazole) (Ayub and Levell 1990; Johansson et al. 2002)
Mitotane c (Lin CW et al. 2012)
Omeprazole d (weak inhibitor) (Dowie et al. 1988)
Natural compounds:
1α,25-Dihydroxyvitamin D3 d (Lundqvist et al. 2010)
Alkylresorcinols c (Ayub and Levell 1990; Oskarsson and Ohlsson Andersson 2016)
Polyphenols d (e.g., apigenin, genistein, hesperitin, naringenin, apigenin, eriodictyol, daidzein, resveratrol (Hasegawa et al. 2013; Lin CJ et al. 2014)
Physiological compounds:
ent-Progesterone e (Auchus et al. 2003)
Other compounds:
2,3,7,8-Tetrabromodibenzo-p-dioxin c (Ding et al. 2007)
5-(Phenoxymethyl)-1,3-dioxane analogs d (Schroeder et al. 2016)
Brominated flame retardants c (2,6-dibromophenol, 2,4,6-tribromophenol, 2,3,7,8-tetrabromodibenzofuran) (Ding et al. 2007)
Crude sediment extracts f (containing high concentrations of polycyclic aromatic hydrocarbons (PAHs) and moderate amounts of polychlorinated biphenyls and organochlorine pesticides) (Blaha et al. 2006)
Prochloraz d (Ohlsson et al. 2009)
YZ5ay (imidazole biphenyl derivative b (Dragan et al. 2006)
Induction: causes cortisol overproduction
Inducers:
Natural compound:
Forskolin g (Asif et al. 2006; Lin CJ et al. 2014)
Physiological compound:
Orexin/hypocretin h (Wenzel et al. 2009)
Other compounds:
Brominated flame retardants g (weak inducer) (e.g., pentabromophenol) (Ding et al. 2007)
Polybrominated diphenyl ethers g (e.g., 2´-hydroxy-BDE-68) h (Song et al. 2008)
Polybrominated biphenyls g (e.g., 3,3´,4,4,5,5´´-tetrabromobiphenyl, 3,3´,4,4´-tetrabromobiphenyl) (Ding et al. 2007)

Footnotes:

^aIrreversible binding the iron heme complex, inactivator

^bCompetitive inhibition, ligand binding

^cReduced/suppressed mRNA and/or protein level/expression and activity

^dDecreased/suppressed/inhibited activity/product formation

^eCompetitive inhibition, binding to enzyme active site

^fGene downregulated/suppressed

^gIncreased transcription/mRNA/protein expression/levels /and/or catalytic activity

^hUp-regulation of biosynthesis, increased expression of protein