Dehydroepiandrosterone sulfate indirect

Metabolic studies carried out with isotopically labeled dehydroepi-androsterone sulfate [312] showed that this conjugated steroid may follow an indirect metabolic pathway initiated by the hydrolysis of the sulfate group. In the course of the metabolism the conjugated steroid thus becomes a free steroid first and the free steroid may undergo further metabolism. On the other hand, dehydroepiandrosterone sulfate may follow a direct metabolic pathway without a break of the ester group. 

The discovery of dehydroepiandrosterone sulfate secretion gave a new incentive to the whole study of conjugation, and it soon became evident that dehydroepiandrosterone sulfate could not only be biosynthesized from sulfo conjugated percursors along a direct biosynthetic pathway, but could also undergo further metabolism, with or without hydrolysis of the sulfate moiety (i.e., indirect or direct metabolism) and act as a privileged precursor of active steroids. 

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. 6. 3a- H- C-dehydroepiandrosterone sulfate. Direct pathway to H- C-epiandrosterone sulfate, and indirect major pathway to C-epiandrosterone sulfate.

Indirect and direct metabolism of dehydroepiandrosterone sulfate are combined in estrogen formation during pregnancy, since dehydroepiandrosterone sulfate is hydroxylated into 16a-hydroxydehydroepiandrosterone... 

Testosterone sulfate does not seem to be hydrolyzed in the organism, but its direct metabolites have not been identified, as only 3.5% of the radioactivity was found in urine after radioactive testosterone sulfate administration. Unlike dehydroepiandrosterone sulfate, testosterone sulfate is not transformed by indirect metabolism into estrogens during pregnancy (Dray, 1963). 

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