HSD17B3

HSD17B3, or Hydroxysteroid 17-Beta Dehydrogenase 3, is a human gene that encodes for the enzyme 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3). This enzyme plays a crucial role in steroid hormone biosynthesis, specifically in the conversion of androstenedione to testosterone in the testes.

The 17β-HSD3 enzyme is primarily expressed in the gonads (testes in males and ovaries in females) and is an NADPH-dependent oxidoreductase. It catalyzes the reduction of the 17-keto group of androstenedione, a weak androgen, to the 17β-hydroxyl group, forming testosterone, the primary male sex hormone.

Mutations in the HSD17B3 gene are the most common cause of 17β-hydroxysteroid dehydrogenase type 3 deficiency, a rare autosomal recessive disorder affecting sex development. Affected individuals typically have a 46,XY karyotype (genetic male) but exhibit ambiguous genitalia at birth, often with female or predominantly female external genitalia. Internally, they possess testes. At puberty, due to increased testosterone production by alternative pathways and conversion in peripheral tissues, affected males typically develop virilization, including deepening of the voice, increased muscle mass, and growth of body hair.

Diagnosis of 17β-hydroxysteroid dehydrogenase type 3 deficiency often involves hormonal analysis, genetic testing to identify mutations in the HSD17B3 gene, and potentially imaging studies. Management may include hormone replacement therapy and surgical correction of ambiguous genitalia.

The HSD17B3 gene is located on chromosome 17q21.33. Its protein product is a member of the short-chain dehydrogenase/reductase (SDR) superfamily.