17HydroxysteroidDehydrogenase

17-Hydroxysteroid dehydrogenases (HSD17B) are a family of NAD(P)H-dependent oxidoreductase enzymes that catalyze the reversible interconversion of 17β-hydroxy steroids and their 17-keto precursors. This activity regulates the local and systemic levels of active sex steroids, influencing androgen and estrogen biosynthesis in both gonadal and non-gonadal tissues.

The HSD17B family comprises multiple isoforms, designated HSD17B1 through HSD17B14 in humans and other species, each with distinct tissue distributions and substrate specificities. Together, they participate in both activation and inactivation steps that shape hormone availability in organs such as the liver, adipose tissue, brain, and gonads.

Notable members include HSD17B1, which activates estrone to estradiol; HSD17B2, which inactivates estradiol to estrone; and HSD17B3, which converts androstenedione to testosterone in the testes. Other enzymes in the family act on a range of 17-hydroxy steroids and related substrates, contributing to broader aspects of steroid metabolism beyond gonadal function.

17-hydroxy steroids, such as 17-hydroxyprogesterone, arise in steroidogenesis and have clinical relevance. Serum levels of 17-hydroxyprogesterone are used as biomarkers in screening for congenital adrenal hyperplasia and related endocrine disorders, reflecting upstream pathway activity that involves HSD17B-mediated steps.

Mutations or altered expression of HSD17B enzymes can impact sexual development and hormone-dependent diseases. For example, HSD17B3 deficiency can cause undervirilization in 46,XY individuals, while other isoforms may influence the risk or progression of estrogen- or androgen-related conditions. Ongoing research aims to clarify isoform-specific roles and therapeutic potential of modulating HSD17B activity.