Lysophosphatidic acid antagonizes the morphoregulatory effects of the luteinizing hormone on luteal cells: Possible role of small Rho-G-proteins

Lysophosphatidic acid (LPA) is a biologically active phospholipid recently introduced as a new marker for ovarian cancer, Because high concentrations of LPA have also been found in the follicular fluid from healthy subjects, one can presume that this biological mediator may have relevance for normal ovarian physiology as well, We have reported earlier that luteal cells pos sess specific binding sites for LPA, Using these cells as a model, we show now that PPA is able to modulate the morphological cell shape changes induc ed by LH in that it inhibits the formation of stellate processes induced by LH. This morphoregulatory effect of LPA is mimicked by cytotoxic necrotizi ng factor 1, a bacterial toxin known to activate small C-proteins from the Rho family. On the of her hand, C3-exotransferase that acts mainly through the inhibition of Rho A mimics the effects of LH, Furthermore, we report he re that the morphoregulatory effects of LPA ape accompanied by the transloc ation of Rho proteins from the cytosol to cell membrane, an effect generall y considered to be an indicator for the activation of Rho-GTPases. During t he development and rescue of the corpus luteum, major morphoregulatory effe cts are exerted by LH that appear to be modulated by LPA via an activation of Rho proteins.