Mode of action of erythropoietin and glucocorticoids on the hepatic erythroid precursor cells: role of prostaglandins.
The hypothesis that prostaglandins, and especially PGE2, are the second messengers of erythropoietin (Ep) and that glucocorticoids inhibit Ep action by inhibiting PG synthesis was tested on the erythroid cell line from fetal rat liver. The optimal (10(-9) M) stimulatory concentration of PGE2 did not reproduce, by far, the maximal effect of Ep on the growth of CFUE erythroid colonies. Ep did not increase PGE2 release in liquid culture media of cell suspensions made of the whole erythroid line or enriched (over 85%) in precursor cells. Ep did not modify the turnover rate of arachidonate. Nevertheless, indomethacin partially inhibited Ep effect on CFUE development, and this inhibition was abolished by PGE2. These results suggest that PGE2 potentiates Ep action but is not its second messenger. Spontaneous PGE2 release in liquid culture media brought about concentrations of the order of 10(-9) M, and 10(-7) M dexamethasone completely inhibited this release. Part of (but not all) the anti-Ep effects of glucocorticoids might thus be mediated this way. Dexamethasone effects required previous protein synthesis.
Mayeux
P
P
Billat
C
C
Felix
J M
JM
Jacquot
R
R
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D003114:Colony-Forming Units Assay; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000037:antagonists & inhibitors / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007213:Indomethacin / Q000494:pharmacology; D008099:Liver / Q000166:cytology*; D011458:Prostaglandins E / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D005938:Glucocorticoids; D011458:Prostaglandins E; D004921:Erythropoietin; D016718:Arachidonic Acid; D003907:Dexamethasone; D015232:Dinoprostone; D007213:Indomethacin