Mechanism of action of gonadotropin-releasing hormone stimulated Leydig cell steroidogenesis. III. The role of arachidonic acid and calcium/phospholipid dependent protein kinase.
Gonadotropin-releasing hormone agonist (GnRHa) markedly increased testosterone formation from 2.35 +/- 0.13 ng/ml of the controls to 14.92 +/- 0.33 ng/ml (mean +/- SE) in isolated and purified rat Leydig cells. GnRHa-induced testosterone formation was completely blocked by phospholipase A2 inhibitor (chloroquin, 10(-4) M), but was potentiated by the addition of either cyclo-oxygenase inhibitor (indomethacin) or lipoxygenase inhibitor (nordihydroguaiaretic acid, NDGA). Arachidonic acid also directly stimulated Leydig cell steroidogenesis and activated Ca/phospholipid dependent protein kinase. Steroidogenic effects of arachidonic acid were also potentiated by the addition of either indomethacin or NDGA. These results suggest that arachidonic acid may be important in mediating direct stimulatory effects of GnRH on Leydig cell steroidogenesis, and the conversion of arachidonic acid to either prostaglandins or leukotrienes is not required for its steroidogenic effect.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009637:Masoprocol; D010703:Phorbol Esters / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000096:biosynthesis*
D001095:Arachidonic Acids; D002396:Catechols; D010703:Phorbol Esters; D010743:Phospholipids; D010906:Pituitary Hormone-Releasing Hormones; D016718:Arachidonic Acid; D013739:Testosterone; D009637:Masoprocol; D002738:Chloroquine; D011494:Protein Kinases; D002118:Calcium; D007213:Indomethacin