3β-hydroxysteroid dehydrogenase

Enzyme involved in steroid biosynthesis

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Structure of 3β-HSD

Identifiers
EC number	1.1.1.145
CAS number	9028-66-2
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

3β-Hydroxysteroid dehydrogenase (3β-HSD) is an enzyme that plays a crucial role in the biosynthesis of all classes of hormonal steroids, including progesterone, androgens, estrogens, glucocorticoids, and mineralocorticoids. It is a member of the oxidoreductase family, specifically acting on the CH-OH group of donors with NAD+ or NADP+ as acceptors.

Function

3β-HSD catalyzes the conversion of Δ5-3β-hydroxysteroids to Δ4-3-ketosteroids. This reaction is essential in the steroidogenesis pathway, where it facilitates the conversion of pregnenolone to progesterone, 17α-hydroxypregnenolone to 17α-hydroxyprogesterone, dehydroepiandrosterone (DHEA) to androstenedione, and androstenediol to testosterone.

Isoenzymes

There are two main isoenzymes of 3β-HSD in humans, encoded by the genes HSD3B1 and HSD3B2.

• HSD3B1 is primarily expressed in the placenta and peripheral tissues.
• HSD3B2 is expressed in the adrenal glands and gonads, where it is involved in the production of steroid hormones.

Clinical Significance

Mutations in the HSD3B2 gene can lead to a rare form of congenital adrenal hyperplasia (CAH), characterized by a deficiency in 3β-HSD activity. This condition results in impaired production of glucocorticoids, mineralocorticoids, and sex steroids, leading to a variety of symptoms including ambiguous genitalia in genetic females, salt-wasting crises, and adrenal insufficiency.

Biochemical Pathway

3β-HSD is involved in the steroidogenesis pathway, which is the process by which cholesterol is converted into steroid hormones. The enzyme acts early in this pathway, following the conversion of cholesterol to pregnenolone by cholesterol side-chain cleavage enzyme.

Inhibition and Regulation

3β-HSD activity can be inhibited by various compounds, which can be useful in the treatment of hormone-dependent conditions such as prostate cancer and breast cancer. Regulation of 3β-HSD is complex and involves multiple factors, including hormonal regulation by adrenocorticotropic hormone (ACTH) and luteinizing hormone (LH).

Research and Developments

Recent studies have focused on the role of 3β-HSD in various diseases, including its potential involvement in polycystic ovary syndrome (PCOS) and its role in the development of adrenocortical carcinoma.

Also see

• Steroidogenesis
• Congenital adrenal hyperplasia
• Androgen
• Estrogen
• Progesterone