Metabolites testosterone

The groups of steroids present will be discussed under the following headings 3j8-hydroxy-A steroids, progesterone and progesterone metabolites, cortisol and its metabolites, testosterone and the 17-OS, and the estrogens. 

BCRP (ABCG2) Cisplatin, folate, methotrexate, mitoxantrone, topotecan, irinotecan, steroids (cholesterol, testosterone, progesterone), certain chlorophyll metabolites, and others... 

In vivo studies in animals suggest that endosulfan may disrupt normal reproductive hormone levels in male animals, but that it is not an endocrine disrupter in females. Persistent depressed testicular testosterone was seen in male rats after intermediate duration oral exposures to endosulfan. In ovariectomized female rats, orally administered endosulfan did not induce normal development of female reproductive tissues, and in female mice and immature female rats, acute parenteral exposure to endosulfan did not affect several endocrine-related end points. In vitro studies have evaluated endosulfan for estrogen receptor (ER) and cytosolic protein binding affinity, ER-mediated reporter gene expression, estrogenic induction of cell proliferation, and alteration of relative abundance of active estradiol metabolites. Overall, in vitro evidence in favor of endosulfan estrogenicity indicates relatively weak potency compared to 17[3-estradiol. Apparently contradictory results were reported in different... 

The metabolism of trichloroethylene, as measured by the levels of excreted urinary metabolites, differs significantly between men and women, although study results are inconsistent (Inoue et al. 1989 Kimmerle and Eben 1973b Nomiyama and Nomiyama 1971). It does appear, however, that women excrete more urinary TCA than do men (Kimmerle and Eben 1973b Nomiyama and Nomiyama 1971). Testosterone has been implicated as a factor in the lower absorption of trichloroethylene in male rats compared with females (Kadry et al. 1991b McCormick and Abdel-Rahman 1991), and the same effect may occur in humans. 

An in vitro study demonstrated decreased testosterone output by Leydig cells with addition of TOCP (Chapin et al. 1990), and suggested that the TOCP metabolite, saligenin cyclic-o-tolyl phosphate, may be the responsible agent for eliciting this effect. 

Recently, Voogt et al. [91] have reported on the d5-pathway in steroid metabolism of Asterias rubens. These workers established the existence of the d5-pathway (Scheme 20), analogous to the pathway found in mammals this conclusion was based on the observation that radiolabeled cholesterol (1) was converted to pregnenolone (112), 17a-hydroxypregnenolone (141), and androstenediol (142). Labeled pregnenolone was converted additionally to progesterone (129). Androstenediol (142) was the main metabolite of de-hydroepiandrosterone (143), a reaction catalyzed by 17/i-hydroxysteroid dehydrogenase (17/1-HSD). The metabolic conversion of androstenedione (131) to testosterone (132) is also mediated by 17/J-HSD and is related to... 

Schulte, B.A. and Rasmussen, L.E.L. (1999a) Musth, sexual selection, testosterone and metabolites. In R.E Johnston, D. Miiller-Schwarze and P. Sorensen (Eds.), Advances in Chemical Communication in Vertebrates, Plenum Press, New York, pp. 383-397. 

FIGURE 4.20 Structures of the CYP3A4 substrates, erythromycin, nifedipine, testosterone, and midazolam, and their metabolites. 

High concentrations of radioactivity were observed in body fat and livers of rats, mice, and squirrel monkeys given oral doses of 60 mg/kg " C-labeled chloroform (Brown et al. 1974a). The maximum levels of radioactivity in the blood appeared within 1 hour and were 3 pg equivalents chloroform/mL for mice and 10 pg equivalents chloroform/mL for monkeys, which represented -0.35 and 1%, respectively, of the total radioactivity. In monkeys, bile concentrations peaked within 6 hours. The distribution of radioactively labeled chloroform was studied in three strains of mice (Taylor et al. 1974). No strain-related differences were observed however, higher levels of radioactivity were found in the renal cortex of males and in the liver of females. The renal binding of radioactive metabolites may have been altered by variations in the testosterone levels as a result of hormonal pretreatment in females or castration in males. Sex-linked differences in chloroform distribution were not observed in rats or monkeys (Brown et al. 1974a). Chloroform accumulates in the adipose tissue of rats after oral exposure of intermediate duration (Pfaffenberger et al. 1980). 

Steroid hormones form a group of pollutants that includes natural hormones such as estradiol, testosterone, and their metabolites as well as several synthetic analogues. Steroid hormones used as growth promoters have already been found in water and sediments (Lai et al. 2000 Thorpe et al. 2003), and their adsorption properties on earth materials have been considered. Lee et al. (2003) report batch experiments where simultaneous sorption of three hormones (17- 3-estradiol, 17-a-ethyl estradiol, and testosterone) on four midwestem U.S. soils and a freshwater sediment were performed. Apparent sorption equilibria were reached within a few hours. Sorption isotherms generally were linear for the chemicals studied on one of these soils (Drummer soil), ranged from 23.4 to 83.2 L kg and log ranged... 

Ester hydrolysis does not invariably lead to inactive metabolites, as exemplified by acetylsalicylic acid. The cleavage product, salicylic acid, retains pharmacological activity. In certain cases, drugs are administered in the form of esters in order to facilitate absorption (enalapril enalaprilate testosterone undecanoate testosterone) or to reduce irritation of the gastrointestinal Lullmann, Color Atlas of Pharmacology... 

When rats were administered atrazine in drinking water at 0.1, 0.2, or 0.5 g/1 for 1 or 3 weeks, they excreted as the principal metabolite 2 -chloro-4-ethylamino-6-amino-s-triazine. Atrazine and its metabolites have been shown to alter the activity of some testosterone-metabolizing enzymes in the rat pituitary and hypothalamus and to decrease hormone-receptor binding in the prostate. ... 

Metabolism/Excretion-There are considerable variations in the reported half-life of testosterone, ranging from 10 to 100 minutes. The half-life of testosterone cypionate IM is approximately 8 days for oral fluoxymesterone, it is approximately 9.2 hours and for methyltestosterone it is 2.5 to 3 hours. Inactivation of testosterone occurs primarily in the liver. About 90% of a testosterone dose is excreted in the urine as conjugates of testosterone and its metabolites about 6% of a dose is excreted in the feces. 

C. In adolescent males, testicular testosterone production dramatically rises from prepuberal levels and then declines into adulthood. However, with advancing adulthood there is a drop in the metabolic clearance rate of testosterone, increasing the length of time that testosterone remains in the serum. Evidence of a relatively constant level of serum testosterone is seen in the relative constant levels of urinary 17-ketosteroids, a metabolite of testosterone, from the second to the fifth decade of life. 

Testosterone metabolism. The lipido-ste-rol extract (LSESr, Permixon) was studied in primary cultures of epithelial cells and fibroblasts separated from benign prostate hypertrophy and prostate cancer tissues. The extract inhibited the formation of the T metabolites androstenedione 5 4 and 5 a-DHT The lipophilic extracts of fruits inhibited T 5p-reductase (EC 1.3.99.5) (5(xR). For fatty acid-like 5(xR inhibition a strongly polar end-group and a molecular skeleton allowing nonpolar interactions with the enzyme were required. The result indicated that 5pR activity in prostatic tissue may be influenced by the lipid environ-... 

Testosterone, when administered by mouth, is rapidly absorbed. However, it is largely converted to inactive metabolites, and only about one sixth of the dose administered is available in active form. Testosterone can be administered parenterally, but it has a more prolonged absorption time and greater activity in the propionate, enanthate, undecanoate, or cypionate ester forms. These derivatives are hydrolyzed to release free testosterone at the site of injection. Testosterone derivatives alkylated at the 17 position, eg, methyltestosterone and fluoxymesterone, are active when given by mouth. 

Trenbolone acetate is a synthetic steroid with hormonal activity similar to testosterone but with greater anabolic activity. After administration to cattle, trenbolone acetate is rapidly hydrolyzed to its free hydroxylated form (28). The 17 -OH epimer is the major metabolite occurring in the excreta, bile, and liver. 

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