title: Metabolism of a glutathione conjugate of 2-hydroxyoestradiol-17  in the adult male rat.
abstract: Adult male rats with cannulated or ligated bile ducts were given S-(2-hydroxyoestradiol-1-yl)[(35)S]glutathione, S-(2-hydroxy[6,7-(3)H(2)]oestradiol-1-yl)glutathione or S-(2-hydroxyoestradiol-1-yl)[glycine-(3)H]glutathione by intraperitoneal injection. The recovery of radioactivity in the bile of bile duct-cannulated rats was 33-86% and in the urine of bile duct-ligated rats was 54-105%. Oestrogen thioether derivatives of glutathione, cysteinylglycine, cysteine and N-acetylcysteine were isolated from bile; only the N-acetylcysteine derivatives could be identified in the urine. The steroid moiety was characterized by microchemical tests before and after treatment with Raney nickel: 2-hydroxyoestradiol-17beta was released from the glutathione conjugate, and 2-hydroxyoestrone and 2-hydroxyoestrone 3-methyl ether from the other conjugates. From intact rats the recovery of administered radioactivity was about 15% in the urine and 5% in the faeces over a period of several days and the radioactivity appeared to be largely protein-bound. The results demonstrate that injected oestrogen-glutathione conjugate undergoes conversion into N-acetylcysteine derivatives in vivo. Oestrogen-glutathione conjugates formed in the intact rat may be excreted in an apparently non-steroidal, possibly protein-bound form, which would not be detected by current analytical techniques.
mesh_terms: D000111:Acetylcysteine / Q000032:analysis / Q000652:urine; D000818:Animals; D001646:Bile / Q000032:analysis; D002848:Chromatography, DEAE-Cellulose; D002854:Chromatography, Paper; D003545:Cysteine / Q000032:analysis; D004586:Electrophoresis; D004958:Estradiol / Q000378:metabolism*; D004987:Ethers; D005243:Feces / Q000032:analysis; D005978:Glutathione / Q000032:analysis / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D011485:Protein Binding; D013460:Sulfur Isotopes; D014316:Tritium
chemical_list: D004987:Ethers; D013460:Sulfur Isotopes; D014316:Tritium; D004958:Estradiol; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine