17β-Hydroxysteroid dehydrogenase
(Redirected from
17Beta Hydroxysteroid dehydrogenase
)
17β-Hydroxysteroid dehydrogenase | |||||||||
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Identifiers | |||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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17β-Hydroxysteroid dehydrogenases (17β-HSD, HSD17B) (
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
17β-HSDs have been known to catalyze the following redox reactions of sex steroids:
- 20α-Hydroxyprogesterone ↔ Progesterone
- Androstenediol
- Androstenedione ↔ Testosterone
- 5α-Androstanedione / 3α-Androstanediol / 3β-Androstanediol
- Estrone ↔ Estradiol
- 16α-Hydroxyestrone ↔ Estriol
Activity distribution
Genes
Genes coding for 17β-HSD include:
- 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]
- 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]
- Perrault syndrome (ovarian dysgenesis and deafness).[20]
- 20α-HSDadrenal 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]activity in addition to 17β-HSD activity. Expressed in the
- 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]
- fundus albipunctatus.[25]
- HSD17B11
- HSD17B12
- HSD17B13
- HSD17B14
At least 7 of the 14 isoforms of 17β-HSD are involved in interconversion of
17β-hydroxysteroids.[12]
Overview
# | 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[32] | |
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[33]
| |
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 | 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 | PSDR1, HSD17B15 | SDR | 318 | 14q23-24.3 | ER | Retinoids, androgens | NADPH | Reduction | Retina, prostate, brain, testis | ? | Retinitis pigmentosa[37] |
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.[32][38]
Some inhibitors of 17β-HSD type I have been identified, for example esters of cinnamic acid and various flavones (e.g. fisetin).[39]
See also
References
- PMID 14214322.
- PMID 13549484.
- PMID 13295221.
- PMID 193845.
- PMID 13129261.
- S2CID 54365519.
- ISBN 978-1-4443-1673-5.
- S2CID 54325300.
- ISBN 978-3-642-58616-3.
- ^ PMID 28430630.
- PMID 20172961.
- ^ ISBN 978-1-4557-2758-2.
- S2CID 54341481.
- ^ ISBN 978-1-59259-726-0.
- PMID 26018678.
- PMID 27994658.
HSD17B2 has both anti-estrogenic and anti-androgenic functions.
- ^ ISBN 978-0-323-29738-7.
- ISBN 978-0-323-32195-2.
- PMID 20108182.
- ^ PMID 20673864.
- S2CID 257943362.
- PMID 9712896.
- PMID 9205114.
- PMID 14585311.
- PMID 25820994.
- ^ S2CID 8608312.
- ^ PMID 25007702.
- ISBN 978-0-12-803608-2.
- S2CID 30321495.
- S2CID 26877571.
- S2CID 23767100.
- ^ PMID 26230882.
- S2CID 32062736.
- ^ Samson M, Labrie F, and Luu-The V (23 June 2012). "Characterization of Type 15 17β-Hydroxysteroid Dehydrogenase". Steroid Hormone Biosynthesis & Metabolism (Translational).
- PMID 11245473.
- PMID 12036956.
- PMID 24916380.
- PMID 24974351.
- S2CID 26950431.
External links
- 3(or+17)beta-hydroxysteroid+dehydrogenase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)