In vivo and in vitro effects of gamma-linolenic acid and eicosapentaenoic acid on prostaglandin production and arachidonic acid uptake by human endometrium.
This study examines the effect of a 6 month dietary supplement of either gamma-linolenic acid (GLA) or eicosapentaenoic acid (EPA) on the synthesis of prostaglandins E2 and F2 alpha by the endometrium of women with regular menstrual cycles. Samples of endometrium, obtained pre- and post-treatment, were incubated in vitro for 2 h and the prostaglandins E2 and F2 alpha released into the medium measured by radioimmunoassay. The ability of the tissue to take up 14C-arachidonic acid before and after treatment was also examined. Both GLA and EPA caused a marked decrease in the synthesis of prostaglandins E2 and F2 alpha (P < 0.001) but under the experimental conditions used, there was no consistent effect on arachidonic acid uptake. Body mass index, serum testosterone, fasting insulin and serum sex hormone-binding globulin (SHBG) concentrations did not change during the 6 month treatment period. An effect of GLA and EPA on arachidonic acid uptake into endometrial tissue explants was demonstrated in vitro. In the presence of both GLA and EPA, uptake into phospholipids (particularly phosphatidylcholine) decreased while uptake into triglycerides increased. Free 14C-arachidonic acid levels (that which could not be removed from the tissue by washing) also increased. Suppression of endometrial prostaglandin E2 and F2 alpha synthesis following GLA or EPA supplementation can be explained as direct competition between these fatty acids and arachidonic acid (the precursor of 2-series prostaglandins) for incorporation into membrane phospholipids. The amount of arachidonic acid available for 2-series prostaglandin synthesis will therefore be reduced. However, other mechanisms may exist which need to be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
Graham
J
J
Unit of Metabolic Medicine, St Mary's Hospital Medical School, London, UK.
Franks
S
S
Bonney
R C
RC
D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D004041:Dietary Fats / Q000494:pharmacology*; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008563:Membrane Lipids / Q000378:metabolism; D009924:Organ Culture Techniques; D010743:Phospholipids / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood; D014280:Triglycerides / Q000378:metabolism; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D004041:Dietary Fats; D007328:Insulin; D008563:Membrane Lipids; D010743:Phospholipids; D012738:Sex Hormone-Binding Globulin; D014280:Triglycerides; D016718:Arachidonic Acid; D013739:Testosterone; D017965:gamma-Linolenic Acid; D015118:Eicosapentaenoic Acid; D015237:Dinoprost; D015232:Dinoprostone