life. 5α-R1 and 5α-R2 are also expressed, although to different degrees in liver, genital and nongenital skin, prostate, epididymis, seminal vesicle, testis, ovary, uterus, kidney, exocrine pancreas, and the brain. In adulthood, 5α-R1-3 is ubiquitously expressed. Substrates Specific substrates include testosterone, progesterone, androstenedione, epitestosterone, cortisol, aldosterone, and deoxycorticosterone. Outside of dihydrotestosterone, much of the physiological role of 5α-reduced steroids is unknown. Beyond reducing testosterone to dihydrotestosterone, 5alpha-reductase enzyme isoforms I and II reduce progesterone to dihydroprogesterone (DHP) and deoxycorticosterone to dihydrodeoxycorticosterone (DHDOC). In vitro and animal models suggest subsequent 3alpha-reduction of DHT, DHP and DHDOC lead to steroid metabolites with effects on cerebral function achieved by enhancing GABAergic inhibition. These neuroactive steroid derivatives enhance GABA via allosteric modulation at GABA(A) receptors and have anticonvulsant, antidepressant and anxiolytic effects, and also alter sexual and alcohol related behavior. 5α-dihydrocortisol is present in the aqueous humor of the eye, is synthesized in the lens, and might help make the aqueous humor itself. Allopregnanolone and THDOC are neurosteroids, with the latter having effects on the susceptibility of animals to seizures. In socially isolated mice, 5α-R1 is specifically down-regulated in glutamatergic pyramidal neurons that converge on the amygdala from cortical and hippocampal regions. This down-regulation may account for the appearance of behavioral disorders such as anxiety, aggression, and cognitive dysfunction. 5α-dihydroaldosterone is a potent antinatriuretic agent, although different from aldosterone. Its formation in the kidney is enhanced by restriction of dietary salt, suggesting it may help retain sodium as follows: {Substrate} + {NADPH} + H+ -> {5\alpha-substrate} + NADP+ 5α-DHP is a major hormone in circulation of normal cycling and pregnant women. Testosterone 5α-Reductase is most known for converting testosterone, the male sex hormone, into the more potent dihydrotestosterone: The major difference is the Δ4,5 double-bond on the A (leftmost) ring. The other differences between the diagrams are unrelated to structure. List of conversions The following reactions are known to be catalyzed by 5α-reductase: Cholestenone → 5α-Cholestanone Progesterone → 5α-Dihydroprogesterone 3α-Dihydroprogesterone → Allopregnanolone 3β-Dihydroprogesterone → Isopregnanolone Deoxycorticosterone → 5α-Dihydrodeoxycorticosterone Corticosterone → 5α-Dihydrocorticosterone Aldosterone → 5α-Dihydroaldosterone Androstenedione → 5α-Androstanedione Testosterone → 5α-Dihydrotestosterone Nandrolone → 5α-Dihydronandrolone Structure 5α-Reductase is a membrane bound enzyme that catalyzes the NADPH dependent reduction of double bonds in steroid substrates to increase potency. The crystal structure of a homolog of 5α-reductase isoenzymes 1 and 2 has been found in Proteobacteria (proteobacteria 5α-reductase). This exists as a monomer with a seven alpha-helix transmembrane