HSD3B2

3β-Hydroxysteroid dehydrogenase type II
Identifiers
Symbol	?
HGNC	5205
OMIM	613890
RefSeq	NM_000198
UniProt	P26439
Other data
EC number	1.1.1.145
Search for Structures Swiss-model Domains InterPro

HSD3B2 (3β-Hydroxysteroid dehydrogenase type II) is an enzyme that plays a crucial role in the biosynthesis of steroid hormones. It is encoded by the HSD3B2 gene located on chromosome 1 in humans. This enzyme is part of the 3β-hydroxysteroid dehydrogenase family, which is involved in the conversion of Δ5-3β-hydroxysteroids into Δ4-3-ketosteroids, a critical step in the production of all classes of steroid hormones, including glucocorticoids, mineralocorticoids, androgens, and estrogens.

Function

HSD3B2 is primarily expressed in the adrenal glands and gonads, where it catalyzes the conversion of pregnenolone to progesterone, 17α-hydroxypregnenolone to 17α-hydroxyprogesterone, dehydroepiandrosterone (DHEA) to androstenedione, and androstenediol to testosterone. These reactions are essential for the synthesis of cortisol, aldosterone, and sex steroids.

Clinical Significance

Mutations in the HSD3B2 gene can lead to a rare form of congenital adrenal hyperplasia (CAH), known as 3β-hydroxysteroid dehydrogenase deficiency. This condition is characterized by impaired production of adrenal and gonadal steroids, leading to symptoms such as ambiguous genitalia in genetic males, salt-wasting crises, and adrenal insufficiency. Diagnosis is typically confirmed through genetic testing and hormonal assays.

Pathophysiology

In 3β-hydroxysteroid dehydrogenase deficiency, the impaired function of HSD3B2 results in decreased levels of cortisol and aldosterone, leading to increased ACTH secretion and adrenal hyperplasia. The accumulation of steroid precursors can also result in increased production of androgens, contributing to the virilization seen in affected individuals.

Research and Therapeutic Implications

Research into HSD3B2 has implications for understanding steroidogenesis and its disorders. Therapeutic approaches for managing 3β-hydroxysteroid dehydrogenase deficiency include glucocorticoid and mineralocorticoid replacement therapy to manage adrenal insufficiency and prevent salt-wasting crises.

Also see

• Steroidogenesis
• Congenital adrenal hyperplasia
• Adrenal gland
• Endocrinology