HSD17B1: Referred to as "estrogenic". Major subtype for activation of estrogens from weaker forms. 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. 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. Said to be responsible for 17β-HSD activity in the endometrium and placenta. Mutations and associated congenital deficiency have not been reported in humans. However, local deficiency in expression of HSD17B2 has been associated with endometriosis.
HSD17B3: Referred to as "androgenic". Major subtype in males for activation of androgens from weaker forms. Also activates estrogens from weaker forms to a lesser extent. 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 type III deficiency. Males with this condition have pseudohermaphroditism, while females are normal with normal androgen and estrogen levels.
HSD17B6: Has activity and catalyzes conversion of the weak androgen androstanediol into the powerful androgen dihydrotestosterone in the prostate gland. May be involved in the pathophysiology of.
HSD17B7: Is involved in cholesterol metabolism but is also thought to activate estrogens and inactivate androgens. Expressed in the ovaries, breasts, placenta, testes, prostate gland, and liver.
HSD17B8: Inactivates estradiol, testosterone, and dihydrotestosterone, though can also convert estrone into estradiol. Expressed in the ovaries, testes, liver, pancreas, kidneys, and other tissues.
At least 7 of the 14 isoforms of 17β-HSD are involved in interconversion of 17-ketosteroids and 17β-hydroxysteroids.
Overview
Clinical significance
Mutations in HSD17B3 are responsible for type III deficiency. Inhibitors of 17β-HSD type II are of interest for the potential treatment of osteoporosis. Some inhibitors of 17β-HSD type I have been identified, for example esters of cinnamic acid and various flavones.
