Alteration of prostaglandin production and agonist responsiveness by n-6 polyunsaturated fatty acids in endometrial cells from late-gestation ewes (original) (raw)

2004, Journal of Endocrinology

We investigated the effect of n-6 polyunsaturated fatty acids (PUFAs) on prostaglandin (PG) production by the uterus. A mixed population of endometrial cells (epthelium and stroma) from late-gestation ewes were cultured in defined medium containing linoleic acid (LA, 18:2, n-6), -linolenic acid (GLA, 18:3, or arachidonic acid (AA, 20:4, in concentrations of 0 (control), 20 or 100 µM. After 45 h in test medium with or without added PUFAs, cells were challenged with control medium (CM), oxytocin (OT, 250 nM), lipopolysaccharide (LPS, 0·1 µg/ml) or dexamethasone (DEX, 5 µM) for 22 h in the continued presence of the same concentration of PUFA and the medium was collected for measurement of PGF 2 and PGE 2 . Supplementation with LA inhibited the production of PGF 2 but did not alter PGE 2 , whereas GLA and AA increased production of both PGs. All PUFA supplements thus increased the ratio of PGE 2 to PGF 2 (E:F ratio) two-to threefold. In control cells, OT and LPS challenges stimulated the production of PGF 2 and PGE 2 . In all challenge groups, the concentrations of PGF 2 in response to PUFAs followed the same pattern -LA<control<GLA<AA -but there were significant alterations in responsiveness as a result of PUFA treatment. In the cells supplemented with 100 µM AA, there was no further increase in PGF 2 output in the presence of OT or LPS and when 100 µM GLA was present neither LPS nor OT stimulated PGE 2 significantly. When LPS was given to AA-supplemented cells, the E:F ratio was increased. DEX did not change PGE 2 production in control or LA-treated cells, but the cells produced significantly less PGF 2 , so the E:F ratio was increased. In contrast, in GLA-and AA-treated cells, DEX reduced the production of both PGF 2 and PGE 2 , so the E:F ratio was unaltered. In summary, the study showed altered production of PGs in the presence of different PUFAs according to their position in the n-6 metabolic pathway. The type of PUFA present affected responsiveness to OT, LPS and DEX and also changed the ratio of PGE 2 to PGF 2 produced. The possible implications of this work are discussed in relation to the effect of diet on term and pre-term labour, which both require upregulation of the endometrial PG synthetic pathway.