title: Bioconversion of 2 alpha-hydroxyprogesterone to 2-hydroxylated corticosteroids by newborn rat adrenal cells in primary culture.
abstract: The bioconversion of 2 alpha-hydroxyprogesterone into 2-hydroxylated steroids was accomplished using newborn rat adrenal cells in primary culture. The products were purified using column and thin-layer chromatography, and identified by GC-MS. They resulted principally from the enzymatic reactions of 21-hydroxylation, 11 beta-hydroxylation, reduction of 20-oxo and 3-oxo groups, and epimerization of the substrate. In addition, minor metabolites resulted from 18-hydroxylation, 6 beta-hydroxylation and reduction of the 3-oxo-4-ene group. The identification of these compounds allowed us to conclude that the metabolism of 2 alpha-hydroxyprogesterone is similar to that of progesterone in this cellular system. Assuming that the 2 beta-epimers of the different metabolites arose principally from the transformation of 2 beta-hydroxyprogesterone, the specificity of the various enzyme systems seems to be similar for both epimers except in the case of the 11 beta-hydroxylation where the reaction appears stereospecific for the 2 beta-epimer. The 2 alpha-hydroxyl group on ring A seems to favor the reduction of the 3-oxo group and it does this stereospecifically to the 3 beta-structure. The epimerization of the substrate, which is most likely enzymatically induced, is the first example of steroid epimerization reported in the adrenal. This is a practical preparative method for synthesizing a variety of steroids hydroxylated at C-2 from a single substrate and could be adjusted to the production of important quantities of 2-hydroxylated metabolites of corticosteroids.
mesh_terms: D004092:20-alpha-Dihydroprogesterone / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis* / Q000302:isolation & purification; D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001711:Biotransformation; D002478:Cells, Cultured; D008401:Gas Chromatography-Mass Spectrometry; D007700:Kinetics; D010084:Oxidation-Reduction; D011374:Progesterone / Q000031:analogs & derivatives*; D051381:Rats
chemical_list: D000305:Adrenal Cortex Hormones; D004092:20-alpha-Dihydroprogesterone; D011374:Progesterone