Testosterone reduction

Figure 8.17 Reaction mechanism of testosterone reduction to dihydrotestosterone (DHT) as catalyzed by the enzyme steroid 5a-reductase.

Li YF, Ramdhan DH, Naito H et al (2011) Ammonium perfluorooctanoate may cause testosterone reduction by adversely affecting testis in relation to PPAR alpha. Toxicol Lett 205(3) 265-272... 

Ketonic carbonyl groups are commonly encountered in steroids and their reduction is facile, even in the absence of an alcohol. The lithium-ammonia reduction of androsta-l,4-diene-3,17-dione affords androst-4-ene-3,17-dione in 20% yield but concurrent reduction of the C-17 ketone results in formation of testosterone in 40% yield, even though the reduction is performed rapidly at —40 to —60° and excess lithium is destroyed with solid ammonium chloride. Similar reduction of the C-17 carbonyl group has been observed in other compounds. In the presence of an alcohol, a ketone is complete-... 

In pyridine, as in 2-propanol, the selectivity of reduction favors the A" -3-ketone over the 17- and 20-ketones.Kupfer suggests that resonance interactions between the double bond and the 3-ketone are smaller in pyridine and in 2-propanol than in methanol. However, by slow addition (1 hour) of one equivalent of NaBH4 in pyridine to a solution of androst-4-ene-3,17-dione i n methanol, testosterone has been obtained in good yield (72 %). Similarly,... 

The properties of chlorine azide resemble those of bromine azide. Pon-sold has taken advantage of the stronger carbon-chlorine bond, i.e., the resistance to elimination, in the chloro azide adducts and thus synthesized several steroidal aziridines. 5a-Chloro-6 -azidocholestan-3 -ol (101) can be converted into 5, 6 -iminocholestan-3l -ol (102) in almost quantitative yield with lithium aluminum hydride. It is noteworthy that this aziridine cannot be synthesized by the more general mesyloxyazide route. Addition of chlorine azide to testosterone followed by acetylation gives both a cis- and a trans-2iddMct from which 4/S-chloro-17/S-hydroxy-5a-azidoandrostan-3-one acetate (104) is obtained by fractional crystallization. In this case, sodium borohydride is used for the stereoselective reduction of the 3-ketone... 

GuiUette, Jr., L.J., Pickford, D.B., and Crain, D.A. et al. (1996). Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment. General and Comparative Endocrinology 101, 32-42. 

Testosterone is metaboHzed by two pathways. One involves oxidation at the 17 position, and the other involves reduction of the A ring double bond and the 3-ketone. Metabohsm by the first pathway occurs in many tissues, including liver, and produces 17-ketosteroids that... 

Formal isomerization of the double bond of testosterone to the 1-position and methylation at the 2-position provides yet another anabolic/androgenic agent. Mannich condensation of the fully saturated androstane derivative 93 with formaldehyde and di-methylamine gives aminoketone 94. A/B-trans steroids normally enolize preferentially toward the 2-position, explaining the regiospecificity of this reaction. Catalytic reduction at elevated temperature affords the 2a-methyl isomer 95. It is not at all unlikely that the reaction proceeds via the 2-methylene intermediate. The observed stereochemistry is no doubt attributable to the fact that the product represents the more stable equatorial isomer. The initial product would be expected to be the p-isomer but this would experience a severe 1,3-diaxial non-bonded interaction and epimerize via the enol. Bromination of the ketone proceeds largely at the tertiary carbon adjacent to the carbonyl (96). Dehydrohalogenation... 

Permethrin may behave like estrogen in females but antiandrogen in males when administered to immature female and male rats at 10-800 mg/kg [154]. Treatment of rats with permethrin at 10 mg/kg/day during gestation produced fetal death and feminization of male fetuses [155]. Reductions in sperm count and motility and in serum testosterone were noted in a 6-week repeated dose study in mice at 35 mg/kg/day. Permethrin may cause mitochondrial membrane impairment in Leydig cells, resulting in inhibition of testosterone biosynthesis [156]. 

Researchers discovered that MPA also had effects on men. When injected into a man, MPA accelerates the metabolism of testosterone while also suppressing its production. The result is a reduction of up to 75 percent in the amount of testosterone in the man s body, thus lowering the intensity of inappropriate sexual cravings and the frequency of unacceptable erotic pre-... 

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