20alpha-hydroxysteroid dehydrogenase explained

Ec Number:	1.1.1.149
Cas Number:	9040-08-8
20-α-hydroxysteroid dehydrogenase
Go Code:	0047006

In enzymology, a 20-α-hydroxysteroid dehydrogenase is an enzyme that catalyzes the chemical reaction

17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)⁺

\rightleftharpoons 17alpha-hydroxyprogesterone + NAD(P)H + H⁺

The 3 substrates of this enzyme are 17alpha,20alpha-dihydroxypregn-4-en-3-one, NAD⁺, and NADP⁺, whereas its 4 products are 17-alpha-hydroxyprogesterone, NADH, NADPH, and H⁺.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is 20alpha-hydroxysteroid:NAD(P)⁺ 20-oxidoreductase. Other names in common use include 20alpha-hydroxy steroid dehydrogenase, 20alpha-hydroxy steroid dehydrogenase, 20alpha-HSD, and 20alpha-HSDH. This enzyme participates in c21-steroid hormone metabolism.

20alpha-HSD has been initially described as a progesterone metabolizing enzyme of the ovary. On a functional level, ovarian 20alpha-HSD is actively involved in the control of progesterone homeostasis in pregnancy of rats and mice. While 20alpha-HSD expression and activity is downregulated in the corpus luteum of pregnancy, 24 hrs prior to parturition ovarian 20alpha-HSD activity is acutely stimulated. Accordingly, in mice with targeted deletion of the 20alpha-HSD gene, progesterone blood concentration remain high throughout pregnancy which results in a delay of 2–4 days in parturition. Indicating that expression of 20alpha-HSD activity is mandatory for the induction of parturition through reduction of progesterone blood concentration. In mice, 20alpha-HSD is also expressed in the adrenals, kidneys, brain, thymus, T cells and bone marrow. Its induction in hematopoietic cells was used as an assay for the identification of T cell derived factor interleukin-3. In addition, the enzyme reduces and inactivates 17-deoxycorticosterone, the precursor of aldosterone and corticosterone.

Structural studies

As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes (AKR1C1),, and .

AKR1C1, AKR1C2, and AKR1C3

Enzymes

AKR1C1 has high catalytic efficiency as a 20α-HSD and AKR1C2 and AKR1C3 efficiently catalyze this reaction as well.^[1]

See also

• 3β(or 20α)-hydroxysteroid dehydrogenase

Further reading

• Shikita M, Inano H, Tamaoki B . 1967 . Further studies on 20-alpha-hydroxysteroid dehydrogenase of rat testes . Biochemistry . 6 . 1760 - 4 . 4382486 . 10.1021/bi00858a026 . 6 .
• Strickler RC, Tobias B, Covey DF . 1981 . Human placental 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase. Two activities at a single enzyme active site . J. Biol. Chem. . 256 . 316 - 21 . 6935192 . 1 . 10.1016/S0021-9258(19)70137-9 . free .
• Wiest WG, Kidwell WR, Balogh K . Progesterone catabolism in the rat ovary: a regulatory mechanism for progestational potency during pregnancy . Endocrinology . 82 . 4 . 844–59 . April 1968 . 5742200 . 10.1210/endo-82-4-844.
• Wiest WG . On the function of 20 alpha-hydroxypregn-4-en-3-one during parturition in the rat . Endocrinology . 83 . 6 . 1181–4 . December 1968 . 5721991 . 10.1210/endo-83-6-1181.
• Piekorz RP, Gingras S, Hoffmeyer A, Ihle JN, Weinstein Y . Regulation of progesterone levels during pregnancy and parturition by signal transducer and activator of transcription 5 and 20alpha-hydroxysteroid dehydrogenase . Mol. Endocrinol. . 19 . 2 . 431–40 . February 2005 . 15471942 . 10.1210/me.2004-0302 . free .
• Akinola LA, Poutanen M, Vihko R, Vihko P . Expression of 17beta-hydroxysteroid dehydrogenase type 1 and type 2, P450 aromatase, and 20alpha-hydroxysteroid dehydrogenase enzymes in immature, mature, and pregnant rats . Endocrinology . 138 . 7 . 2886–92 . July 1997 . 9202232 . 10.1210/en.138.7.2886. free .
• Weinstein Y . 20alpha-hydroxysteroid dehydrogenase: a T lymphocyte-associated enzyme . J. Immunol. . 119 . 4 . 1223–9 . October 1977 . 302277 .
• Weinstein Y, Lindner HR, Eckstein B . Thymus metabolises progesterone- possible enzymatic marker for T lymphocytes . Nature . 266 . 5603 . 632–3 . April 1977 . 300849 . 10.1038/266632a0. 1977Natur.266..632W . 4146146 .
• Ihle JN, Keller J, Oroszlan S, Henderson LE, Copeland TD, Fitch F, Prystowsky MB, Goldwasser E, Schrader JW, Palaszynski E, Dy M, Lebel B . Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity . J. Immunol. . 131 . 1 . 282–7 . July 1983 . 6190911 .
• Hershkovitz L, Beuschlein F, Klammer S, Krup M, Weinstein Y . Adrenal 20alpha-hydroxysteroid dehydrogenase in the mouse catabolizes progesterone and 11-deoxycorticosterone and is restricted to the X-zone . Endocrinology . 148 . 3 . 976–88 . March 2007 . 17122075 . 10.1210/en.2006-1100 . free .

Notes and References

1. Byrns MC . Regulation of progesterone signaling during pregnancy: implications for the use of progestins for the prevention of preterm birth . J. Steroid Biochem. Mol. Biol. . 139 . 173–81 . January 2014 . 23410596 . 10.1016/j.jsbmb.2013.01.015 . 23414730 .