17Beta Hydroxysteroid dehydrogenase

17β-Hydroxysteroid dehydrogenase
Identifiers
EC no.1.1.1.51
CAS no.9015-81-0
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

17β-Hydroxysteroid dehydrogenases (17β-HSD, HSD17B) (EC 1.1.1.51), 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.[1][2][3][4][5] This includes interconversion of DHEA and androstenediol, androstenedione and testosterone, and estrone and estradiol.[6][7]

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.

Reactions[]

Steroidogenesis. 17β-HSD visible in bottom-left region.

17β-HSDs have been known to catalyze the following redox reactions of sex steroids:

Activity distribution[]

Distribution of 17β-HSD activities for formation of estradiol versus estrone in human tissues.[8][9]

Genes[]

Genes coding for 17β-HSD include:

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

Overview[]

Comparison and characteristics of human 17β-HSD isoenzymes[27][28][29][30]
# Gene name Synonyms Family Size (AA) Gene location Cellular location Substrate specificities Preferred cofactor Catalytic preference Tissue distribution Expression profile Pathology
1 HSD17B1 SDR 328 17q21.2 Cytosol Estrogens NADH, NADPH Reduction Ovary, endometrium, breast, brain, prostate, placenta Strongly restricted Breast cancer, prostate cancer, endometriosis
2 HSD17B2 SDR 387 16q23.3 ER Estrogens, androgens, progestogens NAD+ Oxidation Liver, intestine, endometrium, placenta, pancreas, prostate, colon, bone Selectively distributed Breast cancer, prostate cancer, endometriosis, osteoporosis[31]
3 HSD17B3 SDR 310 9q22.32 ER Androgens NADPH Reduction Testis, ovary, blood, saliva, skin, adipose tissue, brain, bone Strongly restricted 17β-HSD3 deficiency, prostate cancer[32]
4 HSD17B4 DBP, MFP2 SDR 736 5q23.1 PXS Fatty acids, bile acids, estrogens, androgens NAD+ Oxidation Liver, heart, prostate, testis, lung, skeletal muscle, kidney, pancreas, thymus, ovary, intestine, placenta, brain, spleen, colon, lymphocytes Ubiquitous DBP deficiency, Perrault syndrome, prostate cancer
5 AKR1C3 HSD17B5, PGFS AKR 323 10p15.1 Nucleus, cytosol Androgens, progestogens, estrogens, prostaglandins NADPH Reduction Prostate, mammary gland, liver, kidney, lung, heart, small intestine, colon, uterus, testis, brain, skeletal muscle, adipose tissue Nearly ubiquitous Breast cancer, prostate cancer
6 HSD17B6 SDR 317 12q13.3 Endosomes Retinoids, androgens, estrogens NAD+ Oxidation Liver, testis, lung, spleen, brain, ovary, kidney, adrenal, prostate Selectively distributed ?
7 HSD17B7 SDR 341 1q23.3 PM, ER Cholesterol, estrogens, androgens, progestogens NADPH Reduction Ovary, corpus luteum, uterus, placenta, liver, breast, testis, brain, adrenal gland, small intestine, lung, thymus, prostate, adipose tissue, others Widely distributed Breast cancer
8 HSD17B8 SDR 261 6p21.32 MC Fatty acids, estrogens, androgens NAD+ Oxidation Prostate, placenta, kidney, brain, cerebellum, heart, lung, small intestine, ovary, testis, adrenal, stomach Widely distributed Polycystic kidney disease
9 RDH5 HSD17B9 318 12q13.2 ER Retinoids NADH/NAD+ Reduction / oxidation Retina, liver, adipose tissue, blood, others ? Fundus albipunctatus
10 HSD17B10 MHBD SDR 261 Xp11.2 MC Fatty acids, bile acids, estrogens, androgens, progestogens, corticosteroids NAD+ Oxidation Liver, small intestine, colon, kidney, heart, brain, placenta, lung, ovary, testis, spleen, thymus, prostate, peripheral blood leukocytes Nearly ubiquitous 17β-HSD10 deficiency, MRXS10, Alzheimer's disease
11 HSD17B11 SDR 300 4q22.1 ER, EP Estrogens, androgens NAD+ Oxidation Liver, pancreas, intestine, kidney, adrenal gland, heart, lung, testis, ovary, placenta, sebaceous gland Nearly ubiquitous ?
12 HSD17B12 SDR 312 11p11.2 ER Fatty acids, estrogens, androgens NADPH Reduction Heart, skeletal muscle, liver, kidney, adrenal gland, testis, placenta, cerebellum, pancreas, stomach, small intestine, large intestine, trachea, lung, thyroid, esophagus, prostate, aorta, urinary bladder, spleen, skin, brain, ovary, breast, uterus, vagina Ubiquitous ?
13 HSD17B13 SDR 300 4q22.1 ER, EP ? NAD+? Oxidation? Liver, bone marrow, lung, ovary, testis, kidney, skeletal muscle, brain, bladder, nasal epithelia Strongly restricted ?
14 HSD17B14 SDR 270 19q13.33 Cytosol Estrogens, androgens, fatty acids NAD+ Oxidation Liver, kidney, brain, gallbladder, breast, adrenal, placenta Widely distributed Breast cancer (prognostic)
15 RDH11[33][34][35] PSDR1, HSD17B15 SDR 318 14q23-24.3 ER Retinoids, androgens NADPH Reduction Retina, prostate, brain, testis ? Retinitis pigmentosa[36]

Clinical significance[]

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.[31][37]

Some inhibitors of 17β-HSD type I have been identified, for example esters of cinnamic acid and various flavones (e.g. fisetin).[38]

See also[]

References[]

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External links[]