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.
D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005260:Female; D006900:Hydroxylation; D066298:In Vitro Techniques; D008234:Lynestrenol / Q000378:metabolism*; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D009640:Norethindrone / Q000096:biosynthesis; D011817:Rabbits
D008234:Lynestrenol; D009640:Norethindrone