linoleic-acid and Uterine-Neoplasms

To understand the placental role in the processes responsible for the preferential accumulation of maternal long-chain polyunsaturated fatty acids (LCPUFAs) in the fetus, we investigated fatty acid uptake and metabolism in the human placenta. A preference for LCPUFAs over nonessential fatty acids has been observed in isolated human placental membranes as well as in BeWo cells, a human placental choriocarcinoma cell line. A placental plasma membrane fatty acid binding protein (p-FABP(pm)) with a molecular mass of approximately 40 kDa was identified. The purified p-FABP(pm) preferentially bound with essential fatty acids (EFAs) and LCPUFAs over nonessential fatty acids. Oleic acid was taken up least and docosahexaenoic acid (DHA) most by BeWo cells, whereas no such discrimination was observed in HepG2 liver cells. Studies on the distribution of radiolabeled fatty acids in the cellular lipids of BeWo cells showed that DHA is incorporated mainly into the triacylglycerol fraction, followed by the phospholipid fraction; the reverse is true for arachidonic acid (AA). The greater cellular uptake of DHA and its preferential incorporation into the triacylglycerol fraction suggests that both uptake and transport modes of DHA by the placenta to the fetus are different from those of AA. p-FABP(pm) antiserum preferentially decreased the uptake of LCPUFAs and EFAs by BeWo cells compared with preimmune serum. Together, these results show the preferential uptake of LCPUFAs by the placenta that is most probably mediated via the p-FABP(pm).

Topics: Adult; alpha-Linolenic Acid; Arachidonic Acid; Biological Transport; Carrier Proteins; Choriocarcinoma; Docosahexaenoic Acids; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; Humans; Linoleic Acid; Maternal-Fetal Exchange; Myelin P2 Protein; Neoplasm Proteins; Oleic Acid; Placenta; Pregnancy; Tumor Cells, Cultured; Tumor Suppressor Proteins; Uterine Neoplasms

Twenty-one women were treated with high doses of depot-medroxyprogesterone acetate (1000 mg/week im) for 6 months as part of the treatment of endometrial carcinoma. The relative fatty acid composition of serum lecithin and cholesterol ester were analyzed. In previous studies low doses of medroxyprogesterone acetate (MPA), in contrast to progestins of the 19-nor-testosterone series, have been shown not to affect the fatty acid composition of serum lecithin and cholesterol ester. However, the high doses of MPA used in this study increased linoleic acid and decreased arachidonic and di-homogammalinolenic acids in serum lecithin. The ability of a steroid to induce this shift has been ascribed to its androgenicity. MPA is considered to have weak, if any, such properties. The findings of this study emphasize the necessity to delineate effects on metabolism of different doses and administrative routes of any particular steroid.

Topics: 8,11,14-Eicosatrienoic Acid; Aged; Arachidonic Acid; Arachidonic Acids; Cholesterol Esters; Fatty Acids; Female; Humans; Linoleic Acid; Linoleic Acids; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Palmitic Acids; Phosphatidylcholines; Stearic Acids; Uterine Neoplasms