Testosterone conjugates

Photochemical cyclohex-2-enoneH> bicyclo (3.1.0) hexan-2-one rearrangement irradiation of testosterone acetate, 322 Photochemical rearrangements of cross-conjugated cyclohexadienones and their photoisomers... 

For protection of domestic cattle, feeds should contain <0.05 mg diflubenzuron/kg FW. Cottonseed may be added to cattle diets provided that diflubenzuron concentrations in the seed do not exceed 0.2 mg/kg FW and that cottonseed composes <17% of the total diet bulk (Gartrell 1981). Diflubenzuron causes biochemical upset, as judged by lowered testosterone levels in chickens and rats (USEPA 1979), altered glutathione 5-transferase activity in mouse liver (which adversely affects the ability to detoxify foreign substances by way of conjugation Young et al. 1986), and disrupted hydroxylamine activity in human infants (USEPA 1979). Additional research seems needed on biochemical alterations induced by diflubenzuron. No diflubenzuron criteria are currently recommended for protection of avian and mammalian wildlife. All data available suggest that wildlife species are about as tolerant to diflubenzuron as are domestic poultry and livestock however, the wildlife database seems inadequate for practicable criteria formulation. 

Another feature of diacids of interest in prodrug design is that the free carboxy group of a drug R-COOH can be used to attach an additional carrier group R OH, e.g., R-CO-Cf -Cf -CO-OR. An example of this type has been reported for a lipid conjugate of testosterone, with R = 2-(l,3-dipalmi-toyljglyccryl [133] (see also Sect. 8.2.5). 

G. K. E. Scriba, Synthesis and in vitro Degradation of Testosterone-Lipid Conjugates , Arch. Pharm. 1995, 328, 271 -276. 

This annulation process was of considerable value in early approaches to steroid synthesis. The structural relationship of the bicyclic product obtained here to the male sex hormone testosterone is immediately apparent. Further, the non-conjugated carbonyl is now activating the adjacent carbon that subsequently features in building up the third ring system. 

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. 

Steroids represent another typical class of doping substances. The determination of endogenous steroids (e.g., testosterone), synthetic anabolic steroids, their esters and their conjugates, and corticosteroids by HPLC-MS has been recently object of an exhaustive review [115] and will not be further discussed here. 

The catabolism of plasma testosterone and other androgens occurs primarily in the liver (Fig. 63.3), where they are conjugated into water-soluble compounds that are excreted by the kidney as the urinary 17-ketosteroids. 

Three extrahepatic UGTs exist, and intestinal UGTs have been shown to conjugate testosterone and some estrogens (Czernik et ah, 2000). 

The major pathway for the degradation of testosterone in humans occurs in the liver, with the reduction of the double bond and ketone in the A ring, as is seen in other steroids with a A4-ketone configuration in the A ring. This leads to the production of inactive substances such as androsterone and etiocholanolone that are then conjugated and excreted in the urine. 

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