Linked Life Data

16339389

Source:http://linkedlifedata.com/resource/pubmed/id/16339389

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-2-16
pubmed:abstractText
Fulvestrant (Faslodex) is administered by intramuscular injection and is converted into ketone, sulfate, sulfone and glucuronide metabolites. Glucuronidation, catalyzed by 18 members of the UDP-glucuronosyltransferase (UGT) enzyme family, plays a major role in the elimination of natural estrogens. The present study was aimed at identifying and characterizing human UGT enzymes involved in the glucuronidation of this antiestrogen as well as other synthetic estrogen derivatives with aliphatic chains on the E2 molecule. In contrast to E2, which is conjugated by UGT1A1, -1A3, -1A8, -1A10, and -2B7, fulvestrant is glucuronidated by UGT1A1, -1A3, -1A4, and -1A8. The four UGT1A-fulvestrant conjugating enzymes glucuronidate this substrate at position 3, whereas only UGT1A8 also produces fulvestrant-17-glucuronide. For E2, only UGT1A3 and UGT2B7 are capable to conjugate at 17-hydroxyposition. These observations indicate that addition of an aliphatic chain to the E2 molecule modifies the specificity of the UGT enzymes toward the C18 molecules. To further investigate the specificity of these enzymes, a series of E2 derivatives with aliphatic or phenyl chains at position 2, 7alpha, and 11beta was also tested for its conjugation with human UGT enzymes. It was observed that, in addition to UGT1A3, UGT1A1 and UGT1A8 also played important roles for the glucuronidation of these compounds. This suggests that the basic structure of E2 is one of the major determinants for the glucuronidation catalyzed by this group of enzymes. Considering the high level of UGT1A3 and -1A4 expression in the gastrointestinal tract and mammary gland, our results suggest that fulvestrant can be inactivated both in intestine and in its target tissue.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
908-20
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Inactivation of the pure antiestrogen fulvestrant and other synthetic estrogen molecules by UDP-glucuronosyltransferase 1A enzymes expressed in breast tissue.
pubmed:affiliation
Oncology and Molecular Endocrinology Research Center, Centre Hospitalier Universitaire de Québec Research Center, Faculty of Medicine, Québec City, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't