19 Nortestosterone 17 [BSA]

A synthetic androgen 7 alpha-Methyl-19-nortestosterone (MENT) has a potential for therapeutic use in 'androgen replacement therapy' for hypogonadal men or as a hormonal male-contraceptive in normal men. Its tissue distribution, excretion and metabolic enzyme(s) have not been reported. Therefore, the present study tested the distribution and excretion of MENT in Sprague-Dawley rats castrated 24 h prior to the injection of tritium-labeled MENT (H-3-MENT). Rats were euthanized at different time intervals after dosing, and the amount of radioactivity in various tissues/organs was measured following combustion in a Packard oxidizer. The radioactivity (% injected dose) was highest in the duodenal contents in the first 30 min of injection. Specific uptake of the steroid was observed in target tissues such as ventral prostate and seminal vesicles at 6 h, while in other tissues radioactivity equilibrated with blood. Liver and duodenum maintained high radioactivity throughout, as these organs were actively involved in the metabolism and excretion of most drugs. The excretion of H-3-MENT was investigated after subcutaneous injection of H-3-MENT into male rats housed in metabolic cages. Urine and feces were collected at different time intervals (up to 72 h) following injection. Results showed that the radioactivity was excreted via feces and urine in equal amounts by 30 h. Aiming to identify enzyme(s) involved in the MENT metabolism, we performed in vitro metabolism of H-3-MENT using rat and human liver microsomes, cytosol and recombinant cytochrome P-450 (CYP) isozymes. The metabolites were separated by thin-layer chromatography (TLC). Three putative metabolites (in accordance with the report of Agarwal and Monder [Agarwal AK, Monder C. In vitro metabolism of 7 alpha-methyl-19-nortestosterone by rat liver, prostate, and epididymis. Endocrinology 1988;123:2187-93]), [i] 3-hydroxylated MENT by both rat and human liver cytosol; [ii] 16 alpha-hydroxylated MENT (a polar metabolite) by both rat and human hepatic microsomes; and [iii] 7 alpha-methyl-19-norandrostenedione (a nonpolar metabolite) by human hepatic microsomes, were obtained. By employing chemical inhibitors and specific anti-CYP antibodies, H-3-MENT was found to be metabolized specifically by rat CYP 2C11 and 3-hydroxysteroid dehydrogenase (3-HSD) enzymes whereas in humans it was accomplished by CYP 3A4, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and 3-HSD enzymes. (C) 2008 Elsevier Inc. All rights reserved.

17 beta-Nortestosterone (17 beta N) is illegally used in livestock as a growth promoter and its endogenous production has been described in some animals, such as adult boars. In this paper, the metabolism of 17 beta N in boars has been studied by gas chromatography/mass spectrometry (GC/MS) in order to identify markers of the exogenous administration. Administration studies of intramuscular 17 beta N laurate to male pigs were performed. Free, sulphate and glucuronide fractions of the urine samples were separated and the steroids present were quantified by GC/MS. 17 beta N was detected in some pre-administration samples. After administration, 17 beta N, norandrosterone, noretiocholanolone (NorE), norepiandrosterone, 5 beta-estrane-3 alpha,17 beta-diol and 5 alpha-estrane-3 beta,17 beta-diol were detected in different fractions, being the most important metabolites, 17 beta N excreted as a sulphate and free NorE. Samples collected in routine controls were also analyzed by GC/MS to identify endogenous compounds. 17 beta N, norandrostenedione and estrone were detected in almost all the samples. No other 17 beta N metabolites were detected. According to these results, the detection by GC/MS of some of the 17 beta N metabolites described above, different from 17 beta N, could be indicative of the exogenous administration of 17 beta N to boars. Copyright (C) 2008 John Wiley & Sons, Ltd.