Tamoxifen-induced modification of serum lipoprotein phospholipids in the cockerel.

Abstract

The administration of tamoxifen (Tam), a nonsteroidal antiestrogen, or of a diphenylmethane derivative of Tam that does not bind to the estrogen receptor (DPPE) of cockerels results in a marked decrease in the concentration of serum lipoprotein constituents with an apparent alteration in phospholipid composition. To establish the nature of changes in phospholipids, the molecular species of phosphatidylcholine (PC) and sphingomyelin (Sph) were isolated and characterized. Between 9 and 18 hr following the administration of Tam or DPPE, there was a marked decrease in the proportion of molecular species of serum PC containing C16 and C18 fatty acids, but there was an increase in the proportion of molecular species containing C20 and C22 polyunsaturated fatty acids. Fatty acid analyses revealed that this change was due to an increase in arachidonic and docosahexaenoic acids at the expense of oleic and linoleic acids. These proportional changes were due to an absolute decrease in serum of PC molecular species containing palmitic and stearic acids in association with oleic and linoleic acids with very little change in the absolute concentration of molecular species containing arachidonic and docosahexaenoic acids. By contrast, the composition of Sph, which contained palmitic acid as the major fatty acid, was not altered during treatment. It is concluded that the short-term effect of Tam and DPPE on plasma phospholipids of the cockerel is due to a selective conservation of PC containing long chain polyunsaturated fatty acids.