Differences in the biotransformation of a 17β-hydroxylated steroid, trenbolone acetate, in rat and cow

Abstract

1. The metabolism of trenbolone acetate, 17 beta-acetoxyestra-4,9,11-trien-3-one (TBA), an anabolic compound used as a growth promoter, was compared in rat and cow. 2. [6,7-3H] TBA was injected i.v. into rats and a heifer, and bile was collected for 24 h. In both species, the bile was the major route of excretion. TBA undergoes an extensive hydrolysis to 17 beta-hydroxyestra-4,9,11-trien-3-one and the unchanged compound was not detected, but subsequent major metabolic pathways are different in the two species. 3. In the rat, oxidation of the 17 beta-hydroxyl to the 17-oxo group and hydroxylation in the 16 alpha-position are the major routes. The three major metabolites are 17 beta-hydroxyestra-4,9,11-trien-3-one, 16 alpha, 17 beta-dihydroxyestra-4,9,11-trien-3-one and 16 alpha-hydroxyestra-4,9,11-trien-3, 17-dione. 4. In the heifer, 17 alpha-epimerization is the major pathway and the main metabolite is the 17 alpha-hydroxyestra-4,9,11-trien-3-one. 5. In both species, estra-4,9,11-trien-3,17-dione and the other metabolites, resulting either from hydroxylation in 1, 2, 6 beta, 16 alpha or 16 beta positions, or from aromatization of the A ring, were minor products. 6. Overall, 60% of the 3-oxotriene structures identified in the rat bile were 17 beta-hydroxylated and the remainder were 17-keto metabolites, whereas in the heifer bile 90% were 17 alpha-hydroxylated compounds. 7. Thus, in bovine species, the major pathway is similar to those of testosterone or 17 beta-estradiol which are mainly excreted as their 17 alpha-epimers. The epimerization strongly decreases the biological potency, as with the natural 17 beta-hormones, and leads to detoxication of tissue residues.

Effects of trenbolone acetate and zeranol on protein metabolism in male castrate andfemale lambs

“…TBA is essentially androgenic (Hoffman, 1980). In rats and cows, plasma TBA is deacetylated to trenbolone (Pottier et al 1981), a steroid which has a similar structure to testosterone and has been shown to bind to the rat prostate gland receptor (Raymond et al 1981). Cytosolic receptors for androgenic hormones have been identified in skeletal muscle from rats (Dub6 et al 1976;Snochowski et al 1980), pigs (Snochowski et al 1981 a) and humans (Snochowski et al 198 1 b).…”

Current knowledge on the environmental fate, potential impact, and management of growth-promoting steroids used in the US beef cattle industry

“…Estergreen et al (1977) found that 90% to 96% of progesterone can be excreted in feces and 4% to 10% in urine. Pottier et al (1981) observed 80% excretion of injected radio-labeled trenbolone acetate in the bile. Krzeminski et al (1981) found 87% excretion of radio-labeled melengestrol acetate from the liver where 10% to 17% remained unabsorbed and in the parent form.…”

17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone) exhibits tissue selective anabolic activity: effects on muscle, bone, adiposity, hemoglobin, and prostate

“…17␤-Hydroxyestra-4,9,11-trien-3-one (trenbolone) is a potent synthetic testosterone analog (67) that does not undergo 5␣-reduction to more potent metabolites (46). As such, trenbolone may induce less growth in prostate and other androgenic tissues that highly express 5␣-reductase.…”