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
1MRQ (AKR1C1),
1Q13, and
1Q5M.
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]
^Byrns MC (January 2014). "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.
doi:
10.1016/j.jsbmb.2013.01.015.
PMID23410596.
S2CID23414730.
Further reading
Shikita M, Inano H, Tamaoki B (1967). "Further studies on 20-alpha-hydroxysteroid dehydrogenase of rat testes". Biochemistry. 6 (6): 1760–4.
doi:
10.1021/bi00858a026.
PMID4382486.
Wiest WG, Kidwell WR, Balogh K (April 1968). "Progesterone catabolism in the rat ovary: a regulatory mechanism for progestational potency during pregnancy". Endocrinology. 82 (4): 844–59.
doi:
10.1210/endo-82-4-844.
PMID5742200.
Wiest WG (December 1968). "On the function of 20 alpha-hydroxypregn-4-en-3-one during parturition in the rat". Endocrinology. 83 (6): 1181–4.
doi:
10.1210/endo-83-6-1181.
PMID5721991.