The role of arachidonic acid on LH-stimulated steroidogenesis and steroidogenic acute regulatory protein accumulation in MA-10 mouse Leydig tumor cells.
Metabolic pathways leading to the production of arachidonic acid (AA) and its metabolites have been reported to have modulatory effects on steroidogenesis in a number of cell types. To examine the importance of the arachidonic acid pathway in steroid production and steroidogenic acute regulatory (StAR) protein expression, luteinizing hormones (LH) or N6-2-o-dibutyryl-adenosine-3:5-cyclic monophosphate-(Bt2cAMP) stimulated MA-10 mouse Leydig tumor cells were treated with various concentrations of quinacrine (an inhibitor of arachidonic acid production). Incubation of the cells with quinacrine resulted in dose-dependent decreases in steroid production and StAR protein. Twenty micromolars quinacrine inhibited 92 and 91% of LH-induced progesterone and StAR protein, respectively, and 98 and 90% of Bt2cAMP-induced progesterone and StAR protein. Reversal of this inhibition was obtained by incubation of quinacrine-treated cells with various levels of AA, which resulted in a dose-dependent increase in both steroid and StAR protein levels. Two hundred micromolars of AA rescued 57 and 60% of the LH-induced steroid production and StAR protein, respectively, and 52 and 89% of Bt2cAMP-induced steroid production and StAR protein. These results suggest that the effect of AA on LH- and cAMP-stimulated steroidogenesis is associated with the modulation of StAR protein expression.
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
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Wang
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Walsh
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Stocco
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007984:Leydig Cell Tumor / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D051379:Mice; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D010750:Phosphoproteins / Q000096:biosynthesis*; D011374:Progesterone / Q000096:biosynthesis*; D011796:Quinacrine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000098682:Steroidogenic Acute Regulatory Protein
D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D016718:Arachidonic Acid; D011374:Progesterone; D003994:Bucladesine; D007986:Luteinizing Hormone; D010741:Phospholipases A; D011796:Quinacrine