3-beta-HSD

3-β-HSD (or 3-β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase) is an enzyme that 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. In humans, there are two 3-β-HSD isozymes encoded by the HSD3B1 and HSD3B2 genes, respectively.

It is also known as delta 5-delta 4-isomerase, which 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. 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

Reaction
3-β-HSD belongs to the family of oxidoreductases, to be specific, 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+ $$\rightleftharpoons$$ 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+.

Isozymes
Humans express two 3-β-HSD isozymes, HSD3B1 (type I) and HSD3B2 (type II). 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
3-β-HSD is inhibited by trilostane.

Clinical significance
A deficiency in the type II form through mutations in HSD3B2 is responsible for a rare form of congenital adrenal hyperplasia. 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.