3α-hydroxysteroid dehydrogenase

Enzyme involved in steroid metabolism

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Identifiers
EC number	1.1.1.50
CAS number	9028-66-2
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

3α-Hydroxysteroid dehydrogenase (3α-HSD) is an enzyme that plays a crucial role in the metabolism of steroids. It is involved in the conversion of 3-keto steroids to their corresponding 3α-hydroxysteroids. This enzyme is part of the oxidoreductase family, specifically acting on the CH-OH group of donors with NAD+ or NADP+ as an acceptor.

Function

3α-Hydroxysteroid dehydrogenase is primarily responsible for the conversion of dihydrotestosterone (DHT) to 3α-androstanediol, a less potent androgen. This reaction is important in the regulation of androgen levels in tissues and has implications in conditions such as benign prostatic hyperplasia and prostate cancer.

The enzyme also plays a role in the metabolism of other steroids, including the conversion of progesterone to 3α-hydroxyprogesterone, and the metabolism of bile acids.

Structure

3α-Hydroxysteroid dehydrogenase is a member of the aldo-keto reductase (AKR) superfamily. The enzyme typically functions as a monomer and contains a conserved NAD(P)H binding domain. The active site of the enzyme is highly specific for its steroid substrates, allowing for the precise conversion of 3-keto steroids to 3α-hydroxysteroids.

Clinical significance

Alterations in the activity of 3α-HSD can have significant clinical implications. Overactivity of the enzyme can lead to decreased levels of potent androgens, affecting male sexual development and function. Conversely, reduced activity can result in elevated levels of active androgens, contributing to conditions such as hirsutism and polycystic ovary syndrome (PCOS) in females.

In addition, 3α-HSD is a target for drug development in the treatment of prostate cancer, as inhibiting its activity can reduce the conversion of DHT to less active forms, thereby reducing androgenic stimulation of prostate cancer cells.

Research

Ongoing research is focused on understanding the detailed mechanisms of 3α-HSD action, its regulation, and its role in various diseases. Studies are also exploring the development of specific inhibitors that can modulate the activity of this enzyme for therapeutic purposes.

Also see

• Steroid metabolism
• Aldo-keto reductase
• Dihydrotestosterone
• Prostate cancer
• Benign prostatic hyperplasia