Steroid ester sulfates

The presence of the sulfuryltransferase system for the formation of steroid ester sulfates has been demonstrated in different human and animal tissues (adrenals, liver, kidneys, skin, etc.). Phese steroid ester sulfates act in the intermediate metabolism of steroids and undergo extensive qualitative and quantitative variations during life development and also in some physiopathologicai conditions. On the other hand, steroid glucuronides generally represent the final step in the metabolism of steroids. 

Other studies establish the possibility of transconjugatioa between steroid ester sulfates and steroid glucuronides. Also, circumstantial evidence for the presence of different sulfokinases and sulfatascs has been observed. 

The systematic and common names and abbreviations of the steroids used throughout this text are indicated in Table I. Using this nomenclature, the steroid ester-sulfates and steroid glucuronides are followed by the suffix yl thus, androsterone sulfate is called 17-oxo-5a-androstan-3a-yl-sulfate, and corticosterone-21-glucuronide is ll/3-hydroxy-4-pregnetie-3,20-dion-21 -y l-j8-D-gIucopyranosiduronatc. 

Schwers and Rodesli, 1968), but this placental sulfataso activity is reduced for other steroid ester sulfates such as androsterone-3a -suIfate, eorti-costcrone-21-suIfatc, 16 -hydroxyprogesterone-16-sulfate testosterone-17/3-sulfate (French and Warren, 1966 Pasqualini et al, 1967a,b). 

Placental perfusion with 20 8-dihydropregneiiolone-3i8-su)fate uncovered a significant hydrolytic activity for this ester sulfate but very little progesterone was obtained. On the other hand, when 20a-dihydroproges-terone-20a-sulfate was perfused in term placenta, most of the radioactive material (97%) was recovered as unchanged ester sulfate and no progesterone was detected (Kitchin ei of., 1969). This result confirms the difference in the activity of human placenta sulfatases for different steroid ester sulfates. 

Identification and quantitative determination of different neutral steroid ester sulfates carried out with adrenal and liver tissues from fetuses at 12-17 weeks of gestation establish that tliese tissues form only monosulfates and that in both adrenals and liver pregnenolone sulfate is quantitatively the most important ester sulfate formed (560 fig/100 g of adrenal tissue and 50 gg/100 g of liver). It lias been su ested that the reduction of the ketonic function in Gn or Cso takes place principally in the liver (Huhtaniemi, JjUukkaiiieii, and Vihko, 1970). 

In contrast to the great placental sulfatase activity for steroid ester sulfates with a 3/3-hydroxy-As function, this liydrolytic activity is limited... 

A very high sulfatase activity which permits the hydrolysis of the steroid ester. sulfates involved in estrogen biosynthesis. These ester sulfates arc mainlj dehydroepiandrosterone- and 16 -hydroxyde iydro-epiandrosterono-3 -sulfate. 

Since in placental tissues there is an important suifata-se activity and since the fetal compartment is very active in the formation of steroid ester sulfates, most of tlie steroids transferred from tlie fetus to the placenta are ester sulfates, and vice versa, most of the steroids which cross from the placenta to the fetus are in unconjugated form. 

Steroid glucuronides are transferred more slowly than steroid ester sulfates. 

It has been well established that in adults some steroid ester sulfates act in the biosynthesis and in the intermediate metabolism of stciroid hormones and that steroid glucuronides are genera% the final step in the transformation of steroids. However, as a result of recent work carried out during fetal life in human.s as well as in animals, the possibility is now recognized that steroid ester sulfates play an important biological role in the... 

K5. Klein, G. P., and Giroud, C. J. P., Incorporation of 7a- H-pregnenolone and d KIl-progesterone into corticosteroids and some of their ester sulfates by human newborn adrenal slices. Steroids 9, 113-134 (1967). 

There are many possible explanations for this finding (1) dehydro-epiaiidrosterone sulfate has a longer half-life (0- S hours) than the free dehydroepiaiidrosterone (15-23 minutes) (Vande WTcle et al., 1903) (2) there are different degrees of cell permeability for the free steroid and for the ester sulfate (3) there is a difference in the partition coefficients for these two steroids as well as differences in their solubilities and forms of transport or (4) these steroids are transformed in different compartments of the placenta. 

Testosterone produced by the placenta is transferred to the fetus and is conjugated mainly with sulfuric acid, but in contrast to a high sulfatase activity by the placental tissues for ester sulfates of 3/J-hydroxy-As steroids and for estrogen sulfates, the testosterone sulfate is poorly hydrolyzed by placental tissues (French and Warren, 1966). These results confirm that the sulfatase activity in the placental compartment is conditioned by the structure of the sulfate. In addition, the incubation of testosterone sulfate with a placental microsomal preparation failed to show any formation of estrogens (Cheatum et at., 1968). These last results also agree with the absence of aromatization of testosterone sulfate during pregnancy (Baulieu ef al., 1965). 

In contrast to most it-Cw, A5-C2i or estrogen conjugates, comparative studies with corticosterone and corticosterone-21-sulfate injected into the umbilical vein establish that this ester sulfate is transferred to the mother slightly more quickly than the free hormone (see Section III, D, 3 and Table IV). These studies also demonstrate that the transfer rates of the free corticosteroids from the fetus to the mother are very different after perfusion of corticosterone, cortisol, cortisone, and deoxycortisosterone into the umbilical vein at midgestation, these steroids were transferred very slowly (2-8% of the administered radioactivity is collected in the maternal urine) on the other hand, after tritiated aldosterone was perfused through the umbilical vein, 20 to 30% of the radioactivity was recovered in the maternal urine (Pasqualini, 1970). 

As a result of the prolongation of the deficiency of the 3/3-hydroxy-dehydrogenase, As — A isomerase system after birth, an important quantity of 3 -hydroxy-As steroids is excreted in the urine of newborns. As the 16a-hydroxylase is very active in the first days of life, very little if any dehydroepiandrosterone or dehydroepiandrosterone sulfate is excreted in newborn urine (Migeon et al., 1957b Vestergaard, 1965 Bertrand et al., 1966 Paulsen et al., 1966) on the other hand, the total excretion rate of urinary 16a-hydroxydehydroepiandrosterone is 300-600 )tig/24 hours (Bongiovanni, 1962 Mitchell and Shackleton, 1966 Mitchell, 1967). Cleary and Pion (1968) found these values to be between 0.7 and 3 mg/24 hours in the first 2 days of life. Alost of these steroids arc eliminated as ester sulfates. 

A4 isomerase deficiency in the first period of life, most of the C19 steroids have a Aj-SiQ,Ifia-dihydroxy structure and are excreted in urine principally as ester sulfates. 

Glucuronidation. Complexation of the steroid to glucuronic acid, most predominantiy via the C-3 hydroxyl, leads to a considerable portion of the excreted metabohtes of ah. glucocorticoids. In infants, sulfurylation (formation of a sulfate ester) is also predominant (16). 

Note Flavonoids react with the reagent even at room temperature [1] mycotoxins, steroids, purines, pyrimidines, cardiac glycosides and lipids only react on heating [2, 4-6]. Zirconyl sulfate can be used to replace the zirconyl chloride in the reagent this is reported to result in an increase in the sensitivity to certain groups of substances (e.g. cholesteryl esters, triglycerides) [4]. 

A number of enzymes known as sulfuric ester hydrolases (EC 3.1.6) are able to hydrolyze sulfuric acid esters. They comprise arylsulfatase (sulfatase, EC 3.1.6.1), steryl-sulfatase (steroid sulfatase, steryl-sulfate sulfohydrolase, arylsulfatase C, EC 3.1.6.2), choline-sulfatase (choline-sulfate sulfohydrolase, EC 3.1.6.6), and monomethyl-sulfatase (EC 3.1.6.16). Whereas mono-methyl-sulfatase is highly specific and does not act on higher homologues, arylsulfatase has a broad substrate specificity and is of particular significance in the hydrolysis of sulfate conjugates of phenols, be they endogenous compounds, drugs, or their metabolites [167-169],... 

C. J. Anderson, L. J. H. Lucas, T. S. Widlanski, Molecular Recognition in Biological Systems Phosphate Esters vs. Sulfate Esters and the Mechanism of Action of Steroid Sulfatases , J. Am. Chem. Soc. 1995,117, 3889-3890. 

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