title: Metabolism of lipoidal derivatives of estradiol-17-beta in human mammary cancer tissue and cell lines.
abstract: Estradiol-17 beta (E2) is converted exclusively to intracellular metabolites, termed lipoidal estrogens [long chain fatty acid 17 beta-esters (E2-L)], by human mammary cancer tissue and cell lines. In order to further evaluate the biological role of lipoidal estrogens, rates of saturation of the estrogen receptor (ER) along with formation of [3H]E2-L have been measured in human mammary cancer cells exposed to 5 nM [3H]E2. Extensive specific binding of E2 to ER in MCF-7 cells (approximately 37%) and ZR-75-1 cells (approximately 62%) occurred before appreciable synthesis of E2-L was evident and the maximum level of E2-L attained was only 3-9% of the E2 specifically bound to ER. In these ER positive cell lines, and in the ER negative cell line MDA-MB-231, an initial rise in the rate of E2-L formation was followed by a decrease at approximately 6 min and re-establishment of a new rate, indicating turnover of the E2-L fraction by esterification-de-esterification reactions. This data does not support the concept that E2-L acts in the transport of E2 to nuclear receptors, but rather than liberation of E2 from E2-L could serve to maintain occupancy of ER necessary for initiation of DNA synthesis. The esterase, as studied in pooled human mammary cancer tissue, was found to hydrolyse E2-17 beta-long chain fatty acid esters at different rates--the enzyme being less active towards E2-17 beta-stearate compared to E2-17 beta-oleate, -linoleate and -linolenate. Esterase activity was significantly higher in MDA-MB-231 cells compared to MCF-7 cells. Treatment of MCF-7 cells with E2 did not alter the specific activity of the esterase towards E2-17 beta-oleate as substrate. Similarly, addition of dibutyryl c-AMP to ZR-75-1 cell cultures was without effect on E2-L, both during the time when E2-L was accumulating, or during a subsequent phase when E2-L was decreasing following transfer to medium lacking E2. Calcitonin, which increases endogenous c-AMP in MCF-7 cells, had no effect on E2-L in this latter phase using this cell line. Thus, no evidence could be provided that the esterase was under E2 control, or control by polypeptide hormones which utilize c-AMP as a second messenger.
authors.affiliation: School of Biochemistry, University of New South Wales, Sydney, Australia.
authors.forename: J B
authors.initials: JB
authors.lastname: Adams
authors.forename: R
authors.initials: R
authors.lastname: Vrahimis
authors.forename: C E
authors.initials: CE
authors.lastname: Young
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002460:Cell Line; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D011960:Receptors, Estrogen / Q000378:metabolism; D014316:Tritium
chemical_list: D005227:Fatty Acids; D011960:Receptors, Estrogen; D014316:Tritium; D004958:Estradiol; D003994:Bucladesine; D002116:Calcitonin; D002265:Carboxylic Ester Hydrolases