HPGD

Hydroxyprostaglandin dehydrogenase 15-(NAD) (the HUGO-approved official symbol = HPGD; HGNC ID, HGNC:5154), also called 15-hydroxyprostaglandin dehydrogenase [NAD+], is an enzyme that in humans is encoded by the HPGD gene.[5][6]

HPGD
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHPGD, 15-PGDH, PGDH, PGDH1, PHOAR1, SDR36C1, hydroxyprostaglandin dehydrogenase 15-(NAD), 15-hydroxyprostaglandin dehydrogenase
External IDsOMIM: 601688 MGI: 108085 HomoloGene: 68095 GeneCards: HPGD
Orthologs
SpeciesHumanMouse
Entrez

3248

15446

Ensembl

ENSG00000164120

ENSMUSG00000031613

UniProt

P15428

Q8VCC1

RefSeq (mRNA)

NM_008278

RefSeq (protein)

NP_032304

Location (UCSC)Chr 4: 174.49 – 174.52 MbChr 8: 56.75 – 56.77 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

In melanocytic cells HPGD gene expression may be regulated by MITF.[7]

Functions

15-hydroxy prostaglandin dehydrogenase (HPGD) is an enzyme belongs to the family of oxidoreductases, specifically the short chain dehydrogenase/reductase family 36C member 1.[8] This protein coding gene encodes a member of the short chain alcohol dehydrogenase protein family.[9] HPGD catalyzes the first step in the catabolic pathway of prostaglandins and is therefore responsible for the metabolic/catabolic inactivation of prostaglandins.[10] This inactivation process will oxidize the 15-hydroxyl group of prostaglandins and yield the corresponding 15-keto (oxo) metabolite.[11]

Prostaglandins have a critical role in the signaling pathways that are involved in reproduction (establishment of pregnancy, maintenance of pregnancy, and initiation of labor), blood pressure homeostasis (vasoconstriction and vasodilation), sexual dimorphism, and the immune system (inflammation).[12][13][14][15][16] HPGD is has a critical role in the regulation of prostaglandin expression.

Expression

HPGD RNA-seq was performed in tissue samples from 95 human individuals representing 27 different tissues to determine tissue-specificity of all protein-coding genes.[17] HPGD was expressed in the adrenal, appendix, bone marrow, brain, colon, duodenum, endometrium, esophagus, fat, gall bladder, heart, kidney, liver, lung, lymph node, ovary, pancreas, placenta, prostate, salivary gland, skin, small intestine, spleen, stomach, testis, thyroid, urinary bladder

Defects in 15-HPGD

15-HPGD has an unappreciated role in the maintenance of pregnancy. In mice, 15-HPDG has been shown to have essential roles in prevention of early termination of pregnancy and maternal morbidity.[18] In 15-HPGD knockout mice, early pregnancy termination was detected. 15-HPGD KO mice that were able to establish pregnancy, lost pregnancy by gestation day ~8.5. At time of pregnancy loss, 15-HPGD KO mice have normal levels of PGE2, increased levels of PGF2α and decreasing levels of serum progesterone.[18]

A hypomorphic mutation of 15-HPGD causes mice to enter labor ~ a full day earlier when compared to their wild-type littermates, due to elevated circulating PGF2α concentrations. Furthermore, it was concluded that 15-HPGD has a critical role in determining the timing of labor[19]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000164120 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000031613 - 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. Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jornvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Feb 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chem Biol Interact. 178 (1–3): 94–8. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
  6. "Entrez Gene: HPGD hydroxyprostaglandin dehydrogenase 15-(NAD)".
  7. Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. S2CID 24698373.
  8. "HPGD Gene - GeneCards | PGDH Protein | PGDH Antibody". www.genecards.org. Retrieved 2023-04-17.
  9. "HPGD 15-hydroxyprostaglandin dehydrogenase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-04-17.
  10. Parent, M., Madore, E., MacLaren, L. A., & Fortier, M. A. (2006). 15-Hydroxyprostaglandin dehydrogenase in the bovine endometrium during the oestrous cycle and early pregnancy. Reproduction, 131(3), 573-582.
  11. Ensor, C. M.; Tai, H. H. (1994-09-21). "Bacterial expression and site-directed mutagenesis of two critical residues (tyrosine-151 and lysine-155) of human placental NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1208 (1): 151–156. doi:10.1016/0167-4838(94)90172-4. ISSN 0006-3002. PMID 8086429.
  12. Hizaki, H. et al. Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP(2). Proceedings of the National Academy of Sciences of the United States of America 96, 10501–10506 (1999).
  13. Kobayashi, T. & Narumiya, S. Function of prostanoid receptors: studies on knockout mice. Prostaglandins & other lipid mediators 68-69, 557–573 (2002).
  14. Lim, H. et al. Multiple female reproductive failures in cyclooxygenase 2-defcient mice. Cell 91, 197–208 (1997).
  15. Murata, T. et al. Altered pain perception and infammatory response in mice lacking prostacyclin receptor. Nature 388, 678–682 (1997).
  16. Tomas, D. W. et al. Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2. The Journal of clinical investigation 102, 1994–2001 (1998).
  17. "HPGD Gene Expression - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-04-17.
  18. Roizen, J. D., Asada, M., Tong, M., Tai, H. H., & Muglia, L. J. (2019). Early pregnancy loss in 15-hydroxyprostaglandin dehydrogenase knockout (15-HPGD−/−) mice due to requirement for embryo 15-HPGD activity. Scientific Reports, 9(1), 1-9.
  19. Roizen, J. D. (2008). 15-hydroxyprostaglandin dehydrogenase in mouse pregnancy and parturition (Order No. 3316671). Available from Health Research Premium Collection; ProQuest Dissertations & Theses Global. (304442244).

Further reading
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