17 β- hydroxysteroid dehydrogenases
17 β -hydroxysteroid dehydrogenases (17 β -HSD, HSD17B) are enzymes that catalyze the conversion of the 17- keto group , for example of estrone , into the 17- hydroxyl group (as in estradiol ), or catalyze the reverse reaction.
Characteristics of the 17 β -HSD
So far, 14 types are known, of which 11 were found in humans.
| Type | Locate | alternative name | preferred co-factor | Substrate | Expression |
|---|---|---|---|---|---|
| HSD17B1 | 17q11 | Estradiol-17 β -Dehydrogenase , E17KSR, EDHB17, | NADPH / H + | Estrone >> androstenedione | Gonads, mammary gland, placenta |
| HSD17B2 | 16q24 | E2DH, HSD17 | NAD + | Estradiol, testosterone | Liver, intestine, endometrium, placenta, pancreas, prostate |
| HSD17B3 | 9q22 | Testosterone-17 β -dehydrogenase | NADPH / H + | Androstenedione | Testicles |
| HSD17B4 | 5q21 | MFP-2, DBP | NAD + | Oversized fatty acids, branched fatty acids, bile acids, estrogens (in pigs), androgens (in pigs) | Liver, heart, prostate, testes, lungs, skeletal muscle, kidney, pancreas, thymus, ovary, intestine, placenta, brain, spleen, lymphocytes |
| HsD17B5 | 10p15 | AKR1C3 | NAD (P) H / H + | Androgens, progestins, estrogens, prostaglandins | Prostate, mammary gland, liver, kidney, lungs, heart, small intestine, large intestine, uterus, testicles, brain, skeletal muscle, adipose tissue |
| HSD17B6 | 12q13 | HSE | NAD (P) H / H + | Androgens, estrogens, | Liver, testes, lungs, spleen, brain, ovary, kidney, adrenal gland, prostate |
| HSD17B7 | 1q23 | PRAP | NADPH / H + | Steroids, estrogens, androgens, progestins | Ovary, uterus, placenta, liver, mammary glands, nerve tissue, adrenal gland, small intestine, lungs, thymus, prostate, fatty tissue and others |
| HSD17B8 | 6p21.3 | NAD + | Estrogens, androgens | Prostate, placenta, kidney, brain, cerebellum, heart, lungs, small intestine, ovary, testes, adrenal gland, stomach | |
| ( HSD17B9 ) | 12q13 | RHD5 | |||
| HSD17B10 | Xp11.2 | HADH2, SCHAD, ABAD ERAB, HSDH | NAD + | Short-chain fatty acids, branched fatty acids, bile acids, estrogens, androgens, progestins, corticosteroids | Liver, small intestine, large intestine, kidney, heart, brain, placenta, lungs, ovary, testes, spleen, thymus, prostate, lymphocytes |
| HSD17B11 | 4q22.1 | retSDR2, Pan1b, DHRS8 | NAD + | Estrogens, androgens | Liver, pancreas, intestine, kidney, adrenal gland, heart, lungs, testicles, ovary, placenta, sweat glands |
| HSD17B12 | 11p11.2 | KAR | NADPH / H + | branched and long-chain fatty acids, estrogens, androgens | Heart, skeletal muscle, liver, kidney, adrenal gland, testes, placenta, cerebrum, pancreas, stomach, intestine, windpipe, lungs, thyroid, larynx, prostate, aorta, urinary bladder, spleen, skin, brain, ovary, mammary glands, vagina |
| HSD17B13 | 4q22.1 | SCDR9 | ? | ? | Liver (bone marrow, lungs, ovary, testicles, kidney) |
| HSD17B14 | 19q13.33 | retSDR3, DHSR10 | NAD + | Estigenes, androgens | Brain, liver, placenta, mammary glands |
Crystal structures exist for types HSD17B1 ( 1QYX and 14 others), HSD17B4 ( 1ZBQ partial), HSD17B5 ( 1XF0 ), HSD17B8 ( 2PD6 ), HSD17B10 ( 2O23 and two more), HSD17B11 ( 1YB1 ) and HSD17B14 ( 1YDE ).
17 β- HSD enzymes as regulators of steroid hormone concentration
One of the tasks of 17 β- HSD enzymes is to control the concentration of the active steroid hormones: One enzyme (e.g. type 1 or 7) can produce estradiol from estrone, while other 17 β- HSD enzymes (type 2 or 4) on the other hand, convert estradiol back to the much less effective estrone. The formation of steroid hormones is tissue-specific, whereas the breakdown takes place in many tissues.
Forward reaction: type 1, type 7
⇔ 
Back reaction: type 2, type 4
Estrone is converted into estradiol and vice versa
In the same way, dihydroepiandrosterone becomes androstenediol
Forward reaction: type 1, type 5
⇔ 
Back reaction: type 2, type 4
or androstenedione converted to testosterone and vice versa:
Forward reaction: type 3, type 5
⇔ 
Back reaction: type 2
The co-factors differ for the forward and backward reactions: In the forward reaction, NADPH / H + is involved , in the backward reactions NAD + is involved.
Association of the 17 β- HSD subtypes and their polymorphisms with certain diseases
| Type | Cancer of | Other diseases |
|---|---|---|
| HSD17B1 | Breast, uterus, fibroadenoma, large intestine, prostate, ovary, | Endometriosis, Ovarian Aging, Age at Menopause, Vasomotor Disorders, Mammography Density, Blood Steroid Disorders, Estramustine Phosphate Side Effects, Diabetes, Depression, Cognitive Dysfunction |
| HSD17B2 | Breast, prostate | |
| HSD17B3 | prostate | Polycystic ovarian syndrome , testosterone 17β dehydrogenase deficiency |
| HSD17B4 | lung | D-bifunctional protein deficiency |
| HSD17B5 | Prostate, lungs, urinary bladder | premature puberty, blood steroid disorders, diabetes |
| HSD17B6 | Polycystic Ovarian Syndrome | |
| HSD17B7 | D-bifunctional protein deficiency | |
| HSD17B8 | D-bifunctional protein deficiency | |
| HSD17B19 | HSD10 deficiency |
literature
- Meier M, Möller G, Adamski J: Perspectives in understanding the role of human 17beta-hydroxysteroid dehydrogenases in health and disease . In: Ann. NY Acad. Sci. . 1155, February 2009, pp. 15-24. doi : 10.1111 / j.1749-6632.2009.03702.x . PMID 19250188 .
Individual evidence
- ↑ a b c Moeller G, Adamski J: Integrated view on 17beta-hydroxysteroid dehydrogenases . In: Mol Cell Endocrinol . 301, August, pp. 7-19. doi : 10.1016 / j.mce.2008.10.040 . PMID 19027824 .
- ^ Prehn C, Moeller G, Adamski J: Recent advances in 17beta-hydroxysteroid dehydrogenases . In: J Steroid Biochem Mol Biol . 114, August, pp. 72-77. doi : 10.1016 / j.jsbmb.2008.12.024 . PMID 19444936 .
