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Androgen metabolism in the baboon: a comparison with the human.
Authors:Y Yamamoto  A T Manyon  Y Osawa  R Y Kirdani  A A Sandberg
Affiliation:1. Department of Psychiatry, Columbia University, 1051 Riverside Drive, Unit 66, Office 3705, New York, NY 10032, USA;2. Division on Substance Use Disorders, New York State Psychiatric Institute, Unit 66, Office 3705, New York, NY 10032, USA;3. Department of Psychiatry and Behavioral Sciences, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA;4. Department of Psychiatry, NYU School of Medicine, One Park Avenue, New York, NY 10016, USA;5. Division of Biostatistics, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA;6. Department of Medicine, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA;7. Department of Pharmacy, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA;2. Novosibirsk State University, Novosibirsk, Russia;3. Saint Petersburg State University Hospital, Saint Petersburg, Russia;4. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy;5. Centre for Integrated Critical Care, The University of Melbourne, Melbourne, Australia;1. Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland;2. Department of Psychiatry, Pomeranian University of Medicine, Szczecin, Poland;3. Department of Physiology, Pomeranian University of Medicine, Szczecin, Poland;4. Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA;1. Pantarhei Bioscience, Zeist, The Netherlands;2. Department of Gynecology-Obstetrics, University Hospital CHR Citadelle, Site Sainte Rosalie, Liège, Belgium;3. Department of Laboratory Medicine, University Hospital CHR Citadelle, Liège, Belgium;4. Department of Reproductive Medicine & Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands;5. Department of Psychology, School of Natural Sciences, University of Stirling, Stirling, United Kingdom;1. Department of Physiology, University of Tennessee Health Science Center, Memphis, TN;2. Cleveland Clinic Foundation, Cleveland, OH
Abstract:To study the metabolism of androgens in the baboon, Papio cyanocephalus, and for a comparison with that in a human, a mixture of [3H]-testosterone (T) and [14C]-androst-4-ene-3,17-dione (A) was injected intravenously into (1) a male and a female baboon with biliary (cannulated) fistulas and catheterized for collection of urine, and (2) a normal 59 year old man. The rates and patterns of excretion of both labels were almost identical in baboon and human urine. The latter fluid contained 60% of the administered dose with an additional 20% of the label appearing in baboon bile. The major conjugate types in the urine after fractionation by DEAE-Sephadex A-25 column chromatography were glucosiduronates and sulfates, with a small percent (< 2%) being unconjugated metabolites. Minor amounts of sulfo-glucosiduronates and disulfates were also present in the bile. In baboon urine and bile, glucosiduronates, sulfates and diconjugates, respectively, represented 82–89%, 4–10% and 2–3% of the labeled compounds. The urinary conjugate pattern of the human resembled that of the baboon. The aglycones of the glucuronide fractions were separated by Lipidex 5000 column-, thin layer- and paper chromatography and identified by co-crystallization with standard compounds. The following compounds were identified: androsterone, etiocholanolone, T, epi-testosterone (epi-T), 5α-androstane-3α,17β-diol, 5α-androstane-3α,17α-diol and 5β-androstane-3α,17α-diol. Other polar compounds were not identified. In urine of both baboons, androsterone predominated (both labels) with 5β-androstane-3α,17β-diol being second highest. In bile, the [3H]-labeled latter compound predominated; androsterone was the predominant [14C]-compound. In human urine, etiocholanolone predominated (both labels) with androsterone being second highest (both labels). Thus, with minor exceptions, the excretion, conjugation and quantitative appearance of aglycone metabolites after administration of androgens were similar in baboon and man.
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