HSD17B

17β-hydroxysteroid dehydrogenases (HSD17B) form a family of enzymes that regulate the activity of steroid hormones by catalyzing reversible redox reactions at the 17β-hydroxyl group of steroids. Through these reactions they interconvert 17-keto steroids (such as estrone and androstenedione) and their more active 17β-hydroxyl forms (estradiol and testosterone), thereby influencing the local and systemic balance of estrogens and androgens. The direction of the reaction—oxidation or reduction—depends on the specific enzyme isoform and cellular context.

In humans, the HSD17B gene family comprises several paralogs that encode isozymes with varying tissue distribution, substrate preference, and cofactor dependence. Well characterized members include HSD17B1, HSD17B2, HSD17B3, HSD17B4 and HSD17B5 (the latter also known as AKR1C3). These enzymes are part of the SDR or AKR superfamilies and may act as reductases or dehydrogenases in different tissues, contributing to both estrogen and androgen biosynthesis and metabolism.

Physiological roles of HSD17Bs include regulation of estrogen and androgen bioavailability, which impacts sexual development, fertility, and metabolic processes. Expression patterns differ across tissues such as the liver, adipose tissue, gonads, placenta, breast, and brain, reflecting diverse physiological functions.

Clinical relevance: altered HSD17B activity or expression has been linked to hormone-dependent conditions, including breast and prostate cancers, fertility disorders, and disorders of pubertal timing. Because they modulate active sex steroid levels, HSD17Bs are studied as potential targets for therapeutic intervention and as markers of hormonal status in various diseases.