Metabolism of lynestrenol: characterization of 3-hydroxylation using rabbit liver microsomes in vitro

In spite of the absence of oxygen at C-3, lynestrenol (17 alpha-ethynyl-4-estren-17 beta-ol) has a marked progestational activity. It is known to be metabolized to norethindrone (17 alpha-ethynyl-4-estren-17 beta-ol-3-one) by 3 beta-hydroxylation and dehydrogenation. In the present study this conversion of lynesterol to norethindrone, via the formation of 3 alpha-hydroxylynestrenol, was investigated using rabbit liver microsomes in vitro. Two hydroxylated metabolites, 3 alpha-hydroxy-lynestrenol and 3 beta-hydroxy-lynestrenol were separated and identified by GLC and GC-MS analyses. In the course of incubation, the concentration of 3 alpha-hydroxy-lynestrenol was much higher than that of the 3 beta-hydroxy isomer suggesting that the metabolic pathway in the conversion to norethindrone proceeds predominantly via 3 alpha-hydroxylation of lynestrenol.