Dehydroepiandrosterone 3/3-glucuronide

Formation of sulfates [328] is relatively reversible. This may be due to the fact that the metabolic clearance rate [318] of sulfates is relatively low [389] and their renal excretion inefficient [4]. The conversion of dehydroepiandrosterone sulfate in vivo to androsterone and etiocholanolone glucuronide was demonstrated by Lieberman and co-workers, who administered isotopically labeled dehydroepiandrosterone sulfate and isolated labeled androsterone and etiocholanolone from glucuronicase-hydrolyzed urine [303]. Since in another study by Lieberman [174], the transconjugation from dehydroepiandrosterone sulfate to dehydroepiandrosterone glucuronide without free dehydroepiandrosterone intermediate was declared to be improbable, in vivo equilibrium between dehydroepiandrosterone sulfate and dehydroepiandrosterone seems probable [303]. 

When radioactive tracers of dehydroepiandrosterone and dehydroepiandrosterone glucuronide are injected intravenously, the conversion of both compounds to dehydroepiandrosterone sulfate is nearly equivalent (contribution dehydroepiandrosterone glucuronide/ contribution dehydroepiandrosterone = 0.8). On the other hand, dehydroepiandrosterone glucuronide gives only 10% of the amount of androsterone obtained... 

Fig. 11. Compartmentalization of dehydroepiandrosterone glucuronide metabolism at the molecular and/or anatomical level. Trans = transconjugating (hypothetical) enzyme.

Buiarelli et al. (2004) extended the above analytical approach to many more related steroids when they published a method for the direct analysis of 15 urinary anabolic steroids in a single run, namely T, epitestosterone, dehydroepiandrosterone (DHEA), androsterone, etiocholanolone, their sulfates and their glucuronides (Figure 2,2), They extracted 2 mL of human urine by solid-phase extraction with methanol elution and reconstituted the residue in aqueous methanol in the presence of deuterated internal standards (da-epitestosterone glucuronide, [16,16,17-"H3 testosterone sulfate and [16,16,17-2H3]testosterone), then monitored, for example, mJz. 289-97 and 109 for T and epitestosterone, miz 367-97 for their sulfates, and m/z 463-113 and 287 for their glucuronides. The method does not achieve quantitation, but it allows the estimation of ratios, which makes it possible to monitor the urinary steroid profile, which is useful for monitoring the abuse of anabolic steroids. 

Side chain splitting in the absence of or after hydrox-ylation in position 11 results in an overall increase in 17-ketosteroids, some of which are biologically active (androstenedione, 11 jS-hydroxyandrostene-dione, dehydroepiandrosterone) and are responsible for the virilizing symptoms. Whether or not testosterone is formed in excess in patients with the adrenogenital syndrome is not certain. High levels of testosterone glucuronide have been found in some patients with adrenal hyperplasia. 

Roberts et al. (1961) first described the conversion of dehydroepian-drosterone sulfate into androsterone and 5/3-androsterone glucuronides in vivo, thereby establishing that dehydroepiandrosterone sulfate can be split in vivo and that there is a dynamic equilibrium dehydroepiandrosterone sulfate dehydroepiandrosterone (Fig. 4). The conversion of dehydroepiandrosterone sulfate into androsterone and 5 -androsterone sulfates can only exist via an indirect pathway (Baulieu et al., 1965) (Fig. 5), but dehydroepiandrosterone sulfate can be transformed both directly and indirectly into epiandrosterone sulfate (Fig. 6). 

Fig. 19. Principal pathways in tbe transfer of androgen and eatri on conji tes between the amniotic cavity, fetus, placenta, and mother. (1) Possible alternatives (2) suggested glucuronidase activity- Ei estrone Kt estradiol estriol Ei S estrone sulfate Et-S estradiol sulfate Kj-S estriol sulfate Ei-Glu estrone glucuronide Ei-Glu estradiol glucuronide Ej-Glu estriol glucuronide Ej-S,Glu estriol-3-sulfale, IbiF ucuronide DIIA dehydroepiandrosterone I60-IIO-DHA l6a-hydroxydehydro-epiandrosterone DlIA-5 dehydroepiandrosterone sulfate I6a-I10-D1IA-S 16a-hy-droxydehydroepiandrasterone sulfate.

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