Effects of progesterone metabolites on fatty acids of the hepatic endoplasmic reticulum membranes

The effect of 2 selected progesterone metabolites on the phospholipid fatty acid composition of the liver and microsomal function was studied in the female rat. 16α-Hydroxyprogesterone significantly increased microsomal phospholipid content and the total amount of fatty acids esterified to phospholipids parallel with aminopyrine N-demethylase activity. Phospholipid changes were attributable to phosphatidylcholine and phosphatidylethanolamine. Both saturated and unsaturated fatty acids were enhanced. In contrast, 5β-pregnane-3α-ol-20-one caused a reduction of microsomal phospholipids, phosphatidycholine, together with decreased aminopyrine N-demethylase activity and total microsomal fatty acid content. Pregnanolone decreased both saturated and unsaturated fatty acids and its action on unsaturated acyl components was greater than on the saturated ones. Changes in fatty acids were manifested in palmitic, stearic and lignoceric acids among saturated fatty acids and in palmitoleic, oleic, linoleic, eicosaenoic, eicosadienoic, eicosatrienoic, arachidonic, eicosapentenoic, docosatrienoic, docosapentenoic and docosahexenoic acids among unsaturated ones. Total liver phospholipids were unaltered by either 16α-hydroxyprogesterone or 5β-pregnane-3α-ol-20-one. These test compounds, however, modified total hepatic fatty acid content. 16α-Hydroxyprogesterone increased total fatty acids and both saturated and unsaturated acyl components, whereas 5β-pregnane-3α-ol-20-one decreased these parameters. Major changes were manifested in saturated fatty acids such as stearic, arachidic and lignoceric acids, and in unsaturated ones such as palmitoleic, linoleic, eicosatrienoic and docosapentenoic acids. The action of these compounds on phospholipid fatty acids of hepatic microsomes may be causally related to their effect on drug-metabolizing activity of the endoplasmic reticulum.