Estrogen sulfotransferase in the metabolism of estrogenic drugs and in the pathogenesis of diseases.
Estrogen sulfotransferase
diseases
estrogen
estrogenic drugs
metabolism
phase II enzymes
Journal
Expert opinion on drug metabolism & toxicology
ISSN: 1744-7607
Titre abrégé: Expert Opin Drug Metab Toxicol
Pays: England
ID NLM: 101228422
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
pubmed:
2
3
2019
medline:
4
4
2019
entrez:
2
3
2019
Statut:
ppublish
Résumé
Biotransformation is important in the metabolism of endobiotics and xenobiotics. This process comprises the activity of phase I and phase II enzymes. Estrogen sulfotransferase (SULT1E1 or EST) is a phase II conjugating enzyme that belongs to the family of cytosolic sulfotransferases. The expression of SULT1E1 can be detected in many tissues, including the liver. SULT1E1 catalyzes the transfer of a sulfate group from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to any available hydroxyl group in estrogenic molecules. The substrates of SULT1E1 include the endogenous and synthetic estrogens. Upon SULT1E1-mediated sulfation, the hydrosolubility of estrogens increases, preventing the binding between the sulfated estrogens and the estrogen receptor (ER). This sulfated state of the estrogens is not irreversible, as the steroid sulfatase (STS) can convert sulfoconjugated estrogens to free estrogens. The expression of SULT1E1 is inducible by several diseases that involve tissue inflammation, such as type 2 diabetes, sepsis, and ischemia-reperfusion injury. Areas covered: This systematic literature review aims to summarize the role of SULT1E1 in the metabolism of estrogenic drugs and xenobiotics, and the role of SULT1E1 in the pathogenesis of several diseases, including cancer, metabolic disease, sepsis, liver injury, and cystic fibrosis. Meanwhile, ablation or pharmacological inhibition of SULT1E1 can affect the outcomes of the aforementioned diseases. Expert opinion: In addition to its role in metabolizing estrogenic drugs, SULT1E1 is unexpectedly being unveiled as a mediator for the disease effect on estrogen metabolism and homeostasis. Meanwhile, because the expression and activity of SULT1E1 can affect the outcome of diseases, the same sulfotransferase and the reversing enzymes STS can be potential therapeutic targets to prevent or manage diseases. Accumulating evidence suggest that the physiological and pathophysiological effects of SULT1E1 can be estrogen-independent and it is necessary to elucidate what other possible substrates may be recognized by the enzyme. Moreover, human studies are paramount to confirm the human relevance of the animal studies.
Identifiants
pubmed: 30822161
doi: 10.1080/17425255.2019.1588884
pmc: PMC6428602
mid: NIHMS1523279
doi:
Substances chimiques
Estrogens
0
Xenobiotics
0
Sulfotransferases
EC 2.8.2.-
estrone sulfotransferase
EC 2.8.2.4
Types de publication
Journal Article
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
329-339Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK083952
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117370
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES023438
Pays : United States
Organisme : NIEHS NIH HHS
ID : R35 ES030429
Pays : United States
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