Androsterone sulfate

Recent results indicate that the air-borne steroids 5a-androst-2-en-17p-ol and 5a-androst-2-en-17-one, which are present in the urine of female E. maximus during the luteal phase at levels that are increased 10- to 20-fold, could be responsible for the synchronization of estrus in females living in close social relationships [117]. The ketone has previously been identified as a product of the incubation of androsterone sulfate with human axillary bacterial isolates [118]. 

Although it has been stated that only phenols are conjugated with sulfuric acid,1 three urinary steroid sulfate esters (androsterone sulfate, dehydro-epi-androsterone sulfate, and A 6-aZZo-pregnene-3(/3)-ol-20-one sulfate) have been isolated in which the sulfuric acid is esterified by an alcoholic hydroxyl group.111 It is true that no alcohol administered to... 

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. 

Siiteri, P. K., and MacDonald, P. C., The utilization of circulating dehydroiso-androsterone sulfate for estrogen synthesis during human pregnancy. Steroids 2, 713-730 (1963). 

Gas Chromatographic Determination of Dehydroepiandrosterone Sulfate and Androsterone Sulfate in Human Plasma Proc. Symp. Steroid Hormones, 2nd, Ghent, 1965 (Pub. 1966) 54-61 CA 68 19128y... 

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). 

Some compounds such as androsterone sulfate, do not seem to be hydrolyzed (Baulieu and Michaud, 1961) but must form unlcnown metabolites, since after administration of the radioactive compound less than 20% of the radioactivity was found in 48 hours urine and less than 2% passed into the bile ( Baulieu et al., 1967b). 

R. L. VandeWiele, and S. Lieberman Evidence that steroid sulfates serve as biosynthetic intermediates in vivo conversion of pregnenolone-sulfate-S to dehydroiso-androsterone-sulfate-S . Biochemistry 2, 648 (1963). 

The transformation products introduced during acid hydrolysis are products of dehydration, halogenation, and rearrangement. Dehydration may occur at sites distant from the carbon atom involved in the conjugate as in the formation of A <">-androstene-3a-ol-17-one and -etiocholene-3a-ol-17-one from the corresponding ll 3-hydroxy compounds (83). It may also occur during the course of the hydrolysis of a sulfate ester as in the conversion of androsterone sulfate to A -androstene-17-one (126). 

About 30 years ago, the two most important forms of steroid conjugates were isolated, one linked to sulfuric acid (androsterone sulfate, isolated by Venning et o/., 1942), and the other linked to glucuronic acid (pregnanediol glucuronide, isolated by Odell and Martian, 1936, and estriol glucuronide, isolated by S. L. Cohen et al., 1936). 

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. 

Ifia-Hydroxj dehydroepiandrosterone and 16a-hydroxydehydroepi-androsterone sulfate... 

Dehydroepiandrosterone (DHEA) is a precursor hormone secreted by the adrenal cortex and to a lesser extent by the central nervous system (Chapter 40 The Gonadal Hormones Inhibitors). It is readily converted to androstenedione, testosterone, and androsterone. In peripheral tissues, aromatase converts DHEA to estradiol. In the plasma, DHEA is converted to DHEA sulfate (DHEAS). 

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]. 

Adrenal androgens also have a complex metabolic fate DHEA-S is formed in the adrenal cortex or by sulfokinases in the liver and kidney from DHEA and excreted by the kidney. DHEA and DHEA-S can be metabolized by 7a-and 16a-hydroxylases. 17p-Reduction of both compounds forms A -5-androstenediol and its sulfate. Androstenedione can be metabolized to androsterone after 3a- and 5a-reduction. 5P-Reduction results in the formation of etiocholanolone (see Eigure 51-7). These metabolites are conjugated to glucuronides and sulfates, which are then excreted in the urine. 

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. 

Rll. Roberts, K. D., Vande Wiele, R. L., and Lieberman, 8., The conversion in vivo of dehydroisoandrosterone sulfate to androsterone and etiocholanolone glu-curonidates. J. Biol. Chem. 236, 2213-2215 (1961). 

Testosterone circulating in the blood is mainly metabolized in the liver to androstenedione which is converted via intermediates into androsterone and its 3 isomer. These are then excreted in urine as glucuro-nides or sulfate conjugates. 

Mitamura, K. Nagaoka, Y. Shimada, K. Honma, S. Namiki, M. Koh, E. Mizokami, A. Determination of sulfates of androsterone and epiandrosterone in human serum using isotope diluted liquid chromatography lectrospray ionization-mass spectrometry. Biomed. Chromatogr. 2005, 79(10), 796-801. 

Effective Adsorption of Dehydroepi-androsterone (DHA) Sulfate and Other 17-Ketosteroid Conjugates from Urine by Amberlite Clin. Biochem. 4(4) 287-296 (1971) ... 

Thomas, B. S., and Friedman, M. Determination of Solvolyzed Sulfate Esters of Dehydroepiandrosterone and Androsterone in Human Peripheral Plasma by Gas-Liquid Chromatography... 

Data obtained in vivo (Baulieu et al, 1965) have shown (Fig. 9) that after an injection of radioactive dehydroepiandrosterone and dehydroe-piandrosterone sulfate, the free compound is transformed more rapidly and more eflBciently into androsterone and etiocholanolone than the sulfo conjugate, the latter being apparently protected from rapid liver catabolism. 

Fig. 9. Urinary radioactive androsterone and SjS ndrosterone after injection of C-dehydroepiandrosterone (above) and H-dehydroepiandrosterone sulfate (below) (percentage of the injected radioadtivity).

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... 

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). 

On the other liaiid, in spite of an increase in production of dehydroepi-audrosterone (free or 3/3-sulfate) and lf>a-hydroxydehydroepiandrosterone (free or sulfate) the urinarj- excretion rates of these 17-keto steroids are of the same order as in iionprcgnant women. Similar results were found for the other 17-keto steroids such us androsterone, (Simmer el aJ., 11159). On the other hand, the plasma testosterone concentration increases 30-40 times at the end of gestation (Meeker, 1%(>). 

The saturated Cai compounds are then either conjugated with glucuronic acid and appear in urine as the glucuronides, or they are further broken down. The side chain is split off particularly easily from 17-hydroxy compounds. The products are 17-keto steroids, androsterone, etiocholanolone, and. others, which are also excreted as glucuronides (more rarely as sulfates). The amount of 17-keto steroids in urine can be estimated easily with Zimmermann s color reaction it is useful for the diagnosis of adrenal cortical activity. One should be aware, however, that only a part of the corticosteroid excretion is measured, together vith testosterone inactivation products. Normally, about 10-20 mg per day of 17-keto steroids are excreted. 

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