Estradiol metabolism in Ishikawa endometrial cancer cells.
Estrogen-responsive human cells derived from a specimen of well differentiated endometrial adenocarcinoma (Ishikawa line) were incubated with [3H]estradiol (E2) at various concentrations and the medium was sampled at 3, 6 and 24 h to evaluate the kinetics of removal of the hormone and the formation of unconjugated or sulfated metabolites. The detectable products of metabolism were estrone and the conjugate estradiol-3-sulfate. The latter was identified by high pressure chromatography, before and after acetylation, oxidation, and hydrolysis. The disappearance of [3H]E2 from the medium was found to follow first order kinetics between 3 and 24 h, with half-lives increasing from 4.7 to 53 h as the initial concentrations of the hormone were raised from 10(-8) to 10(-6)M. At the lowest concentration, practically all of the [3H]E2 added to the cultures was converted to estradiol-3-sulfate in 24 h, whereas at 10(-6)M oxidation to estrone was quantitatively more important than sulfation. These results indicate the presence in Ishikawa cells of an estrogen sulfotransferase of low Michaelis constant for E2, and 17 beta-oxidoreductase activity that significantly contributes to the metabolism of E2 only at higher concentrations of substrate.
D000230:Adenocarcinoma / Q000201:enzymology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism*; D004970:Estrone / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D015238:Sulfotransferases; D013466:Sulfurtransferases / Q000378:metabolism; D014594:Uterine Neoplasms / Q000201:enzymology*
D004970:Estrone; C028628:estradiol-3-sulfate; D004958:Estradiol; D013466:Sulfurtransferases; D015238:Sulfotransferases; C020122:estrone sulfotransferase