The protein encoded by this gene is a microsomal enzyme that catalyzes the conversion of the stress hormone cortisol to the inactive metabolite cortisone. In addition, the encoded protein can catalyze the reverse reaction, the conversion of cortisone to cortisol. Too much cortisol can lead to central obesity, and a particular variation in this gene has been associated with obesity and insulin resistance in children. Mutations in this gene and H6PD (hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase)) are the cause of cortisone reductase deficiency. Alternate splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, May 2011]
Function
Controls the reversible conversion of biologically active glucocorticoids such as cortisone to cortisol, and 11-dehydrocorticosterone to corticosterone in the presence of NADP(H) (PubMed:10497248, PubMed:12460758, PubMed:14973125, PubMed:15152005, PubMed:15280030, PubMed:17593962, PubMed:21453287, PubMed:27927697, PubMed:30902677).
Participates in the corticosteroid receptor-mediated anti-inflammatory response, as well as metabolic and homeostatic processes (PubMed:12414862, PubMed:10497248, PubMed:15152005, PubMed:21453287).
Plays a role in the secretion of aqueous humor in the eye, maintaining a normotensive, intraocular environment (PubMed:11481269).
Bidirectional in vitro, predominantly functions as a reductase in vivo, thereby increasing the concentration of active glucocorticoids (PubMed:12414862, PubMed:10497248, PubMed:11481269, PubMed:12460758).
It has broad substrate specificity, besides glucocorticoids, it accepts other steroid and sterol substrates (PubMed:15095019, PubMed:15152005, PubMed:17593962, PubMed:21453287).
Interconverts 7-oxo- and 7-hydroxy-neurosteroids such as 7-oxopregnenolone and 7beta-hydroxypregnenolone, 7-oxodehydroepiandrosterone (3beta-hydroxy-5-androstene-7,17-dione) and 7beta-hydroxydehydroepiandrosterone (3beta,7beta-dihydroxyandrost-5-en-17-one), among others (PubMed:17593962).
Catalyzes the stereo-specific conversion of the major dietary oxysterol, 7-ketocholesterol (7-oxocholesterol), into the more polar 7-beta-hydroxycholesterol metabolite (PubMed:15095019, PubMed:15152005).
7-oxocholesterol is one of the most important oxysterols, it participates in several events such as induction of apoptosis, accumulation in atherosclerotic lesions, lipid peroxidation, and induction of foam cell formation (PubMed:15095019).
Mediates the 7-oxo reduction of 7-oxolithocholate mainly to chenodeoxycholate, and to a lesser extent to ursodeoxycholate, both in its free form and when conjugated to glycine or taurine, providing a link between glucocorticoid activation and bile acid metabolism (PubMed:21453287).
Catalyzes the synthesis of 7-beta-25-dihydroxycholesterol from 7-oxo-25-hydroxycholesterol in vitro, which acts as ligand for the G-protein-coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby regulate immune cell migration (PubMed:30902677).
Involvement in disease
Cortisone reductase deficiency 2 (CORTRD2):
An autosomal dominant error of cortisone metabolism characterized by a failure to regenerate cortisol from cortisone, resulting in increased cortisol clearance, activation of the hypothalamic- pituitary axis and ACTH-mediated adrenal androgen excess. Clinical features include hyperandrogenism resulting in hirsutism, oligo- amenorrhea, and infertility in females and premature pseudopuberty in males.
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