Sulfo conjugates metabolism

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. 

However new questions were asked Are other steroid conjugates secreted How and where are these secreted products biosynthesized and metabolized Are the sulfo conjugates biologically active, and what is their role in hormonal regulation Only a few of these questions can be answered yet. 

In the kidney, one finds glucuronyltransferases (Dutton, 1966) but little or no steroid sulfotransferase (Bostrom and Wengle, 1967), whereas the intestine contains both enzyme systems, sulfotransferases in the intestinal wall (Baulieu et al., 1965) and glucuronyltransferases in the mucosa (Dutton, 1966). As intestinal metabolism of steroids is diflFerent in germ-free and conventional rats (GustafiFson and S jo vail, 1968), in diis animal, microorganisms in the intestine can enhance sulfo conjugation, which in turn, promotes fecal excretion a similar type of mechanism can exist in humans, yet complicated by the presence of bacterial sulfotransferases and sulfatases. 

After the first demonstration of a direct metabolism of a steroid conjugate [androstenediol sulfate =i dehydroepiandrosterone sulfate (Baulieu et ah, 1963)], showing that a 17j8-hydroxysteroid oxidoreductase can have a sulfo conjugate as a substrate, other enzymic transformations of dehydroepiandrosterone sulfate were reported (Fig. 4). Dehydroepiandrosterone sulfate can undergo 16o -hydroxylation to 16a-hydroxy-dehydroepiandrosterone sulfate which can be further hydroxylated into androstenetriol sulfate its direct 17-hydroxylated metabolite, androstene-... 

Sulfo conjugated steroids are only partially excreted in the urine, and are largely metabolized, with or without hydrolysis of the ester bond. 

Most conjugation reactions take place in the liver after being metabolized by reductive enzymes, the steroids are conjugated by sulfo- or glucu-ronyltransferases. The hydrogenated metabolites of corticosteroids and many 3a,5a-reduction products of the pregnane and androstane series. 

---