HSD17B1

17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) is an enzyme that in humans is encoded by the HSD17B1 gene.[5][6][7] This enzyme oxidizes or reduces the C17 hydroxy/keto group of androgens and estrogens and hence is able to regulate the potency of these sex steroids

HSD17B1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHSD17B1, EDH17B2, EDHB17, HSD17, SDR28C1, hydroxysteroid (17-beta) dehydrogenase 1, hydroxysteroid 17-beta dehydrogenase 1, E2DH, 17-beta-HSD, 20-alpha-HSD, Hsd17b1
External IDsOMIM: 109684 MGI: 105077 HomoloGene: 37303 GeneCards: HSD17B1
Orthologs
SpeciesHumanMouse
Entrez

3292

15485

Ensembl

ENSG00000108786

ENSMUSG00000019301

UniProt

P14061

P51656

RefSeq (mRNA)

NM_000413
NM_001330219

NM_010475

RefSeq (protein)

NP_000404
NP_001317148

NP_034605

Location (UCSC)Chr 17: 42.55 – 42.56 MbChr 11: 100.97 – 100.97 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

This enzyme is responsible for the interconversion of estrone (E1) and estradiol (E2) and for the interconversion of androstenedione and testosterone:

17β-estradiol + NADP+ + estrone + NADPH + H+
testosterone + NADP+ + androstenedione + NADPH + H+

The human 17β-HSD1 isozyme is highly specific for estrogens over androgens whereas the rodent isozyme is less specific.[8]

Discovery

Human 17β-HSD1 was the first enzyme of the 17β-HSD family to be cloned and to have its sequence identified.[9][10] Its three-dimensional structure is also the first example of any human steroid-converting enzyme.[11]

Structure

This enzyme contains a short-chain dehydrogenase domain that contains a characteristic 3-layer (αβα) sandwich known as a Rossmann fold. The human enzyme contains 327 amino acids and exists as a homodimer with two identical subunits of 34.5 kDa [10][12] The N-terminal short-chain dehydrogenase domain contains binding site for the NADP+/NADPH cofactor. A narrow, hydrophobic C-terminal domain contains a binding pocket for the steroid substrate.

Clinical significance

Estradiol stimulates while dihydrotestosterone (DHT) inhibits breast cancer growth. Furthermore 17β-HSD1 levels positively correlate with estradiol and negatively correlate with DHT levels in breast cancer cells. Hence 17β-HSD1 represents a possible drug target for breast cancer treatment.[13]

See also

Notes

References

  1. GRCh38: Ensembl release 89: ENSG00000108786 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000019301 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Luu-The V, Labrie C, Simard J, Lachance Y, Zhao HF, Couët J, Leblanc G, Labrie F (Feb 1990). "Structure of two in tandem human 17 beta-hydroxysteroid dehydrogenase genes". Molecular Endocrinology. 4 (2): 268–75. doi:10.1210/mend-4-2-268. PMID 2330005.
  6. Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Mar 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chemico-Biological Interactions. 178 (1–3): 94–8. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
  7. "Entrez Gene: HSD17B1 Hydroxysteroid (17-beta) dehydrogenase 1".
  8. Saloniemi T, Jokela H, Strauss L, Pakarinen P, Poutanen M (2012). "The diversity of sex steroid action: novel functions of hydroxysteroid (17β) dehydrogenases as revealed by genetically modified mouse models". The Journal of Endocrinology. 212 (1): 27–40. doi:10.1530/JOE-11-0315. PMID 22045753.
  9. Luu The V, Labrie C, Zhao HF, Couët J, Lachance Y, Simard J, Leblanc G, Côté J, Bérubé D, Gagné R (Aug 1989). "Characterization of cDNAs for human estradiol 17 beta-dehydrogenase and assignment of the gene to chromosome 17: evidence of two mRNA species with distinct 5'-termini in human placenta". Molecular Endocrinology. 3 (8): 1301–9. doi:10.1210/mend-3-8-1301. PMID 2779584.
  10. Peltoketo H, Isomaa V, Mäentausta O, Vihko R (Oct 1988). "Complete amino acid sequence of human placental 17 beta-hydroxysteroid dehydrogenase deduced from cDNA". FEBS Letters. 239 (1): 73–7. doi:10.1016/0014-5793(88)80548-9. PMID 2846351. S2CID 32468574.
  11. Ghosh D, Pletnev VZ, Zhu DW, Wawrzak Z, Duax WL, Pangborn W, Labrie F, Lin SX (May 1995). "Structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase at 2.20 A resolution". Structure. 3 (5): 503–13. doi:10.1016/S0969-2126(01)00183-6. PMID 7663947.
  12. Lin SX, Yang F, Jin JZ, Breton R, Zhu DW, Luu-The V, Labrie F (Aug 1992). "Subunit identity of the dimeric 17 beta-hydroxysteroid dehydrogenase from human placenta". The Journal of Biological Chemistry. 267 (23): 16182–7. doi:10.1016/S0021-9258(18)41984-9. PMID 1322895.
  13. Aka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX (Apr 2010). "17beta-hydroxysteroid dehydrogenase type 1 stimulates breast cancer by dihydrotestosterone inactivation in addition to estradiol production". Molecular Endocrinology. 24 (4): 832–45. doi:10.1210/me.2009-0468. PMC 5417535. PMID 20172961.

Further reading

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