Changes by progesterone derivatives in fatty acids from phosphatidylcholine and phosphatidylethanolamine fractions in rat liver endoplasmic reticulum.

The effects of two progesterone metabolites on fatty acid composition of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) from total liver and liver microsomes were studied in female rats. 16 alpha-Hydroxyprogesterone significantly increased the amount of fatty acids esterified to PC and PE fractions in total liver and liver microsomes. Both saturated and unsaturated fatty acyl components were enhanced. In contrast, 5 beta-pregnan-3 alpha-ol-20-one caused a reduction of fatty acids bound to PC and PE fractions from total liver and liver microsomes. Pregnanolone decreased both saturated and unsaturated fatty acids. Changes in specific fatty acids occurred in palmitic and stearic acids among saturated components, and palmitoleic, oleic, linoleic, eicosatrienoic, arachidonic and docosahexenoic acids among unsaturated ones. The unsaturated: saturated fatty acid ratio was raised by 16-alpha-hydroxyprogesterone and lowered by 5 beta-pregnan-3 alpha-ol-20-one in all phospholipid fractions. The induction of drug metabolizing enzymes by 16 alpha-hydroxyprogesterone may be related to an enhanced synthesis of microsomal phospholipids containing unsaturated fatty acids, particularly arachidonic and docosahexenoic acids. In contrast, the inhibition of drug metabolism by 5 beta-pregnan-3 alpha-ol-20-one is associated with reduced formation of unsaturated fatty acyl side chains.