3-β-HSD (or 3-β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase) is an enzyme which catalyses the synthesis of progesterone from pregnenolone, 17-hydroxyprogesterone from 17-hydroxypregnenolone, and androstenedione from dehydroepiandrosterone in the adrenal gland. It is the only enzyme in the adrenal pathway of corticosteroid synthesis that is not a member of the Cytochrome P450 family.^[1] In humans, there are two 3-β-HSD isozymes encoded by the HSD3B1 and HSD3B2 genes respectively.

Also known as delta 5-delta 4-isomerase that catalyzes the oxidative conversion of delta 5-3 beta- hydroxysteroids to the delta 4-3-keto configuration and is therefore essential for the biosynthesis of all classes of hormonal steroids, namely progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens.^[2] The 3-beta HSD complex is responsible for the conversion of:

• pregnenolone to progesterone
• 17-alpha-pregnenolone to 17-alpha-progesterone
• dehydroepiandrosterone (DHEA) to androstenedione
• androstenediol to testosterone

[edit] Reaction

3-β-HSD belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. This enzyme participates in c21-steroid hormone metabolism and androgen and estrogen metabolism.

3-β-HSD 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 3 products are 3-oxo-Δ5-steroid, NADH, and H⁺.

[edit] Isozymes

Humans express two 3-β-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.

[edit] 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

[edit] Inhibitors

3-β-HSD is inhibited by trilostane.^[4]

[edit] Biosynthetic pathway

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).

[edit] 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.

[edit] See also

• 3-β(or 20-α)-hydroxysteroid dehydrogenase

[edit] References

[edit] Further reading