17β-Hydroxysteroid dehydrogenase

17β-HSDs catalyze the following redox reactions of sex steroids:^{[citation needed]}

• 20α-Hydroxyprogesterone ↔ Progesterone
• DHEATooltip Dehydroepiandrosterone ↔ Androstenediol
• Androstenedione ↔ Testosterone
• Dihydrotestosterone ↔ 5α-Androstanedione / 3α-Androstanediol / 3β-Androstanediol
• Estrone ↔ Estradiol
• 16α-Hydroxyestrone ↔ Estriol

Activity distribution

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.^[10] Recently, has been found to inactivate DHT into 3α- and 3β-androstanediol.^[10][11] Expressed primarily in the ovaries and placenta but also at lower levels in the breast epithelium.^[12][10] Major isoform of 17β-HSD in the granulosa cells of the ovaries.^[13] Mutations and associated deficiency have not been reported in humans.^[14] Knockout mice show altered ovarian sex steroid production, normal puberty, and severe subfertility due to defective luteinization and ovarian progesterone production.^[15]
• HSD17B2: Describable as "antiestrogenic" and "antiandrogenic".^[16] 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. Preferential activity on androgens. Expressed widely in the body including in the liver, intestines, lungs, pancreas, kidneys, endometrium, prostate, breast epithelium, placenta, and bone.^[10][17][12] Said to be responsible for 17β-HSD activity in the endometrium and placenta.^[18] Mutations and associated congenital deficiency have not been reported in humans.^[14] However, local deficiency in expression of HSD17B2 has been associated with endometriosis.^[19]
• HSD17B3: Referred to as "androgenic". Major subtype in males for activation of androgens from weaker forms (androstenedione to testosterone and DHEA to androstenediol). Also activates estrogens from weaker forms to a lesser extent (estrone to estradiol). This is essential for testicular but not ovarian production of testosterone. Not expressed in the ovaries, where another 17β-HSD subtype, likely HSD17B5, is expressed instead. Mutations are associated with 17β-HSD type III deficiency. Males with this condition have pseudohermaphroditism, while females are normal with normal androgen and estrogen levels.^[17][12]
• HSD17B4: Also known as D-bifunctional protein (DBP). Involved in fatty acid β-oxidation and steroid metabolism (specifically estrone to estradiol, for instance in the uterus).^[20] Mutations are associated with DBP deficiency and Perrault syndrome (ovarian dysgenesis and deafness).^[20]
• HSD17B5: Also known as aldo-keto reductase 1C3 (AKR1C3), encoded by the AKR1C3 gene in humans. Has 3α-HSDTooltip 3α-hydroxysteroid dehydrogenase and 20α-HSDTooltip 20α-hydroxysteroid dehydrogenase activity in addition to 17β-HSD activity. Expressed in the adrenal cortex and may act as the "androgenic" 17β-HSD in ovarian thecal cells. Also expressed in the prostate gland, mammary gland, and Leydig cells.^[12]
• HSD17B6: Has 3α-HSDTooltip 3α-hydroxysteroid dehydrogenase activity and catalyzes conversion of the weak androgen androstanediol into the powerful androgen dihydrotestosterone in the prostate gland. Also involved into a backdoor pathway from 17α-hydroxyprogesterone to dihydrotestosterone by 3α-reduction of a metabolic intermediary, 17α-hydroxydihydroprogesterone, into another intermediary, 17α-hydroxyallopregnanolone.^[21] May be involved in the pathophysiology of PCOSTooltip polycystic ovary syndrome.^[12]
• HSD17B7: Is involved in cholesterol metabolism but is also thought to activate estrogens (estrone to estradiol) and inactivate androgens (dihydrotestosterone to androstanediol).^[12] Expressed in the ovaries, breasts, placenta, testes, prostate gland, and liver.^[12]
• HSD17B8: Inactivates estradiol, testosterone, and dihydrotestosterone, though can also convert estrone into estradiol. Expressed in the ovaries, testes, liver, pancreas, kidneys, and other tissues.^[22][23]
• HSD17B9: Also known as retinol dehydrogenase 5 (RDH5). Involved in retinoid metabolism.^[24] Mutations are associated with fundus albipunctatus.^[25]
• HSD17B10: Also known as 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD). Substrates include steroids, neurosteroids, fatty acids, bile acids, isoleucine, and xenobiotics.^[26][27] Mutations are associated with 17β-HSD type X deficiency (also known as HSD10 disease or MHBD deficiency) and mental retardation, X-linked, syndromic 10 (MRXS10), which are characterized by neurodegeneration and mental retardation, respectively.^[26][27]
• HSD17B11: very little is known on the role/function of this iszyme.^[28][29]
• HSD17B12
• HSD17B13
• HSD17B14

At least 7 of the 14 isoforms of 17β-HSD are involved in interconversion of 17-ketosteroids and 17β-hydroxysteroids.^[12]

Mutations in HSD17B3 are responsible for 17β-HSD type III deficiency.

Inhibitors of 17β-HSD type II are of interest for the potential treatment of osteoporosis.^[34][40]

Some inhibitors of 17β-HSD type I have been identified, for example esters of cinnamic acid and various flavones (e.g. fisetin).^[41]

• Steroidogenic enzyme
• 3α-Hydroxysteroid dehydrogenase