title: The metabolism and hormonal activity of some ring-C aromatic steroids.
abstract: The metabolism and steroid hormonal activity of the ring-C aromatic steroid 20 alpha,21-dihydroxy-17 beta-methyl-18-norpregna-4,8,11,13-tetraen-3-one (20 alpha,21-diol) was studied in rats and mice. The excretion of metabolites following intraperitoneal administration was monitored using tritium-labelled steroid. Of the total radioactivity, 15% was excreted in the urine after 2 days. Biliary excretion was rapid, with 80% of radioactivity collected over 12 h, while 67% was excreted in the faeces after 3 days. The metabolites isolated from bile and urine are conjugates, predominantly glucuronides, while only 5% of the dose was excreted as free unchanged steroid. The aglycones of the main metabolites from bile were identified as unchanged 20 alpha,21-diol and the two steroids 3 alpha,20 alpha,21-trihydroxy-17 beta-methyl-18-nor-5 alpha-pregna-8,11,13-triene and 3 beta, 20 alpha,21-trihydroxy-17 beta-methyl-18-nor-5 alpha-pregna-8,11,13-triene which resulted from reduction of the 4-ene-3-ketone system. Liver glycogen deposition, used as a measure of glucocorticoid activity, was induced in mice by 20 alpha,21-diol but not by its epimer the corresponding 20 beta,21-diol. Only the 20 alpha,21-diol was found to antagonise glycogen deposition when given simultaneously with cortisol. In adrenalectomised rats, the 20 alpha,21-diol produced a significant decrease in urinary Na+ excretion and increased K+ excretion. An equimolar dose of the 20 alpha,21-diol and deoxycorticosterone acetate gave a urinary excretion Na+/K+ ratio which reflected the combined mineralocorticoid effect of each steroid. The 20 beta, 21-diol produced no change in the urinary Na+/K+ ratio.
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D003900:Desoxycorticosterone / Q000494:pharmacology; D005243:Feces / Q000032:analysis; D005965:Glucuronates / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D009652:Norpregnenes / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: C039005:20,21-dihydroxy-17-methyl-18-norpregna-4,8,11,13-tetraen-3-one; D005965:Glucuronates; D009652:Norpregnenes; D003900:Desoxycorticosterone; D006854:Hydrocortisone