Differential effects of lysolipids on steroid synthesis in cells expressing endogenous LPA2 receptor

Lygia T. Budnik and Bärbel Brunswig-Spickenheier

Bioactive Lipids, Institute for Cellular Neurobiology, Anatomie I, University Hospital Eppendorf, Hamburg D-20246

Corresponding Author: l.budnik{at}uke.uni-hamburg.de

Incubation of ovarian luteal cells with bioactive lipid mediator, lysophosphatidic acid (LPA) for 180 min. abolishes gonadotropin-induced steroid production with no attenuation of the cyclic AMP accumulation. Treatment with the lysolipid also diminishes [14C] steroid production in cells preloaded with either [14C] cholesterol or [14C] acetate. Neither the expression of StAR (steroidogenic acute regulatory-protein) protein nor the in vitro steroid synthesis is affected in isolated mitochondrial fractions. The LPA-induced attenuation of the steroid production occurs only during the mid cycle corpus luteum and is associated with a transient endogenous expression of mRNA for the LPA2 receptor (with no concomitant changes in the expression of LPA1 receptor). Expression of LPA2 is accompanied by LPA-induced sphingosine-1-phosphate (S1P) production. Since in the presence of sphingosine kinase inhibitor, dihydrosphingosine, luteal cells can overcome the inhibitory effects of LPA on steroid synthesis, we suggest the possible requirement of intracellular S1P production. Interestingly, no LPA-induced inhibition of 8Br-cAMP stimulated progesterone synthesis can be detected in Leydig tumor cell line, MA10 cells, which is expressing LPA2 receptor only, but no LPA1. Surprisingly however, exogenous S1P is inhibiting agonist stimulated progesterone in both cell types, by inhibiting cyclic AMP accumulation suggesting different mechanisms of action.

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