Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1990-4-20
pubmed:abstractText
Previously, we reported that relatively high micromolar concentrations of the liver tumor promoter 17 alpha-ethinyl estradiol (EE2) stimulated DNA synthesis and enhanced the DNA synthetic response to epidermal growth factor (EGF) in primary cultures of female rat hepatocytes [J.D. Yager, B.D Roebuck, T.L. Paluszcyk, and V.A. Memoli, Carcinogenesis 7, 2007-2014 (1986); Y.E. Shi and J.D. Yager, Cancer Res. 49, 3574-3580 (1989)]. In this study, our goal was to examine the metabolism of EE2 in cultured hepatocytes. After 4, 24, and 48 hr of culture, hepatocytes maintained their ability to convert up to 95% of a 4 nM concentration of [3H]EE2 to polar conjugates within 4 hr. EE2 at 2 microM was also 95% metabolized within 4 hr. HPLC analysis of the metabolites confirmed the rapid disappearance of [3H]EE2 and the formation of polar conjugates as detected by organic extraction. HPLC separation of hydrolyzed conjugates indicated that the major aglycone was the parent compound, EE2. In general, the metabolites differed both qualitatively and quantitatively from those reported in vivo in the rat. The rapid metabolism of EE2 by hepatocytes in culture may, at least in part, explain the high concentrations of EE2 required to stimulate DNA synthesis in cultured hepatocytes and to potentiate the response to EGF.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
486-96
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Metabolism of the liver tumor promoter ethinyl estradiol by primary cultures of rat hepatocytes.
pubmed:affiliation
Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03756.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't