3β-Hydroxysteroid dehydrogenase

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3-beta-HSD
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3β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase
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ExPASy
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KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
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NCBIproteins
3β-Hydroxysteroid dehydrogenase
Identifiers
SymbolHSD3B
PfamPF01073
InterProIPR002225
Membranome245
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Chr. 1 p13-p11
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StructuresSwiss-model
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Chr. 1 p13.1
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3β-Hydroxysteroid dehydrogenase/Δ5-4 isomerase (3β-HSD) (

testis and placenta. In humans, there are two 3β-HSD isozymes encoded by the HSD3B1 and HSD3B2 genes
.

3β-HSD is also known as delta Δ5-4-isomerase, which catalyzes the oxidative conversion of Δ5-3β-

hormonal steroids, namely progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens.[2]

The 3β-HSD complex is responsible for the conversion of:

Reaction

3β-HSD belongs to the family of oxidoreductases, to be specific, those acting on the CH-OH group with NAD+ or NADP+ as acceptor. This enzyme participates in C21-steroid hormone metabolism and androgen and estrogen metabolism.

3β-HSD catalysis|catalyzes the chemical reaction:

a 3β-hydroxy-Δ5-steroid + NAD+ ⇌ a 3-oxo-Δ5-steroid + NADH + H+

Thus, the two substrates of this enzyme are 3β-hydroxy-Δ5-steroid and NAD+, whereas its three products are 3-oxo-Δ5-steroid, NADH, and H+.

Isozymes

Humans express two 3β-HSD isozymes, HSD3B1 (type I) and HSD3B2 (type II).[3] The type I isoenzyme is expressed in placenta and peripheral tissues, whereas the type II 3β-HSD isoenzyme is expressed in the adrenal gland, ovary, and testis.

Nomenclature

The systematic name of this enzyme class is 3β-hydroxy-Δ5-steroid:NAD+ 3-oxidoreductase. Other names in common use include:

  • progesterone reductase
  • Δ5-3β-hydroxysteroid dehydrogenase
  • 3β-hydroxy-5-ene steroid dehydrogenase
  • 3β-hydroxy steroid dehydrogenase/isomerase
  • 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase
  • 3β-hydroxy-Δ5-C27-steroid oxidoreductase
  • 3β-hydroxy-5-ene-steroid oxidoreductase
  • steroid-Δ5-3β-ol dehydrogenase
  • 3β-HSDH
  • 5-ene-3β-hydroxysteroid dehydrogenase
  • 3β-hydroxy-5-ene-steroid dehydrogenase

Inhibitors

3β-HSD is potently inhibited by azastene, cyanoketone, epostane, and trilostane.[4] Medroxyprogesterone acetate and medrogestone are weak inhibitors of 3β-HSD which may substantially inhibit it at high dosages.

Biosynthetic pathway

  • Human steroidogenesis, showing reactions of 3β-HSD near-left in green box.
    Human
    steroidogenesis
    , showing reactions of 3β-HSD near-left in green box.
  • Corticosteroid biosynthetic pathway in the rat, showing reaction catalyzed by 3β-HSD (second arrow from the top).
    Corticosteroid biosynthetic pathway in the rat, showing reaction catalyzed by 3β-HSD (second arrow from the top).

Clinical significance

A deficiency in the type II form through mutations in HSD3B2 is responsible for a

rare form of congenital adrenal hyperplasia.[5]
No human condition has yet been linked to a deficiency in the type I enzyme. Its importance in placental progesterone production expression suggests that such a mutation would be embryonically lethal.

The fetal adrenal cortex lacks expression of the enzyme early on, thus

neonatal respiratory distress syndrome. If delivery is unavoidable (e.g. because of placental abruption, or pre-eclampsia/HELLP syndrome
), then glucocorticoids (e.g. cortisol) can be administered.

See also

References

  1. PMID 3088022
    .
  2. PMID 1737804
    .
  3. PMID 15632317
    .
  4. S2CID 23048546
    .
  5. S2CID 26468595
    .

Further reading
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