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Concept
17β-Hydroxysteroid dehydrogenase
Summary
17β-Hydroxysteroid dehydrogenases (17β-HSD, HSD17B) (), also 17-ketosteroid reductases (17-KSR), are a group of alcohol oxidoreductases which catalyze the reduction of 17-ketosteroids and the dehydrogenation of 17β-hydroxysteroids in steroidogenesis and steroid metabolism. This includes interconversion of DHEA and androstenediol, androstenedione and testosterone, and estrone and estradiol.
The major reactions catalyzed by 17β-HSD (e.g., the conversion of androstenedione to testosterone) are in fact hydrogenation (reduction) rather than dehydrogenation (oxidation) reactions.
17β-HSDs have been known to catalyze the following redox reactions of sex steroids:
20α-Hydroxyprogesterone ↔ Progesterone
() ↔ Androstenediol
Androstenedione ↔ Testosterone
Dihydrotestosterone ↔ 5α-Androstanedione / 3α-Androstanediol / 3β-Androstanediol
Estrone ↔ Estradiol
16α-Hydroxyestrone ↔ Estriol
Genes coding for 17β-HSD include:
HSD17B1: Referred to as "estrogenic". Major subtype for activation of estrogens from weaker forms (estrone to estradiol and 16α-hydroxyestrone to estriol). Catalyzes the final step in the biosynthesis of estrogens. Highly selective for estrogens; 100-fold higher affinity for estranes over androstanes. However, also catalyzes the conversion of DHEA into androstenediol. Recently, has been found to inactivate DHT into 3α- and 3β-androstanediol. Expressed primarily in the ovaries and placenta but also at lower levels in the breast epithelium. Major isoform of 17β-HSD in the granulosa cells of the ovaries. Mutations and associated deficiency have not been reported in humans. Knockout mice show altered ovarian sex steroid production, normal puberty, and severe subfertility due to defective luteinization and ovarian progesterone production.
HSD17B2: Describable as "antiestrogenic" and "antiandrogenic". Major subtype for inactivation of estrogens and androgens into weaker forms (estradiol to estrone, testosterone to androstenedione, and androstenediol to DHEA). Also converts inactive 20α-hydroxyprogesterone into active progesterone.
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