Stimulation of human placental lactogen release by arachidonic acid
Handwerger, S.; Barrett, J.; Barry, S.; Markoff, E.; Zeitler, P.; Cwikel, B.; Siegel, M.
Molecular Pharmacology 20(3): 609-613
1981
ISSN/ISBN: 0026-895X PMID: 6799774 Document Number: 178076
Arachidonic acid at concentrations between 20-300 .mu.M stimulated human placental lactogen (hPL) release from placental explants in a dose-dependent manner (r = 0.90, P < 0.001). Explants incubated for 2 h in medium containing 20 .mu.M arachidonic acid released 97.0 .+-. 12.1% (mean .+-. SE, P < 0.05 more hPL than did control explants; explants incubated in medium containing 300 .mu.M arachidonic acid released 514.2 .+-. 18.7% (P < 0.001) more hPL. Phospholipase A2 (0.11 U/ml). which cleaves arachidonic acid from the 2-acyl position of phospholipids, stimulated hPL release by 2272.6 .+-. 219.6% (P < 0.001). Neither arachidonic acid norphospholipase A2 affected the release of human chorionic gonadotropin, lactic dehydrogenase, or alkaline phosphatase, and arachidonic acid had no effect on the release of trichloroacetic acid-precipitable 35S-labeled proteins. The fatty acid precursors of arachidonic acid (linoleic, .gamma.-linolenic, and dihomo-.gamma.-linolenic acids) also stimulated hPL release, but 11,14,17-icosatrienoic, oleic, and palmitic acids had no statistically significant effects. The cyclo-oxygenase inhibitors indomethacin (14 .mu.M) and flufenamic acid (18 .mu.M) had no effects on either the basal release of hPL or the stimulatory affect of arachidonic acid. The cyclo-oxygenase products prostaglandins E1, E2 and F2.alpha. had no effects on hPL release. The lipoxygenase inhibitors 5,8,11,14-icosatetraynoic acid (82 .mu.M) and BW755C [3-amino-1-[m-(trifluoromethyl)phenyl]-20-pyrazaline] (20 .mu.M) had no effects on basal hPL release but potentiated the stimulatory effect of arachidonic acid. Arachidonic acid may stimulate hPL release via a non-cyclo-oxygenase, non-lipoxygenase pathway.