Reversal of epidermal hyperproliferation in essential fatty acid deficient guinea pigs is accompanied by rapid generation of inositol triphosphate.

This study probes the extent of coupling between the reversal of epidermal hyperproliferation induced by essential fatty acid (EFA) deficiency in guinea pigs, the hydrolysis of epidermal phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P2), and the rapid formation of inositol triphosphate (InsP3). Our data revealed that the incorporation of free [3H]-inositol into phosphatidylinositol 4P and PtdIns4,5P2 of microsomal preparations from hyperproliferative epidermis was markedly elevated when compared with epidermis from normal-fed animals. The reversal of the hyperproliferating epidermis by dietary cross-over supplementations with safflower oil and primrose oil resulted in striking morphological normalization, cellular decrease in epidermal DNA synthesis, decrease in the biosynthesis of 14C-PtdIn4,5P2 from precursor 14C-inositol, and a significant increase in the rapid generation of transient InsP3 by epidermis from the cross-over-fed animals. These findings taken together indicate that the reversal of epidermal hyperproliferation to normal in guinea pig skin and the increased capability of the tissue microsomal preparation to generate InsP3 are linked in this tissue, and raise the possibility that epidermal inositol-phospholipid metabolism may play a role in the pathogenesis of cutaneous hyperproliferative disorders.