Etiocholanolone testosterone

The major pathway for the degradation of testosterone in humans occurs in the liver, with the reduction of the double bond and ketone in the A ring, as is seen in other steroids with a A4-ketone configuration in the A ring. This leads to the production of inactive substances such as androsterone and etiocholanolone that are then conjugated and excreted in the urine. 

Disposition in the Body. Testosterone is the androgenic hormone formed in the testes. In man, it is metabolised to 5a-androstane-3a,17)5-diol, androsterone, etiocholanolone, and 5a-androstene-3,17-dione. In the horse, the major metabolites are 5a-androstane-3)5,17a-diol, which is excreted in the urine as the glucuronide conjugate, and the 17)5-epimer which is excreted in the urine as the sulphate conjugate. 

The composition of the excreted urinary 17-ketosleroids also reveals a close similarity between the hormones of different origin the testis accounts for 30% while the adrenal cortex contributes the remaining 70% of the total urinary 17-ketosteroids [383]. Androsterone, ep a-androsterone, and 5/8-androsterone (etiocholanolone) are the main urinary metabolities of testosterone, and dehydroepiandrosterone is the major urinary 17-ketosteroid derived from the adrenal cortex. 

The bulk of the urinary 17-KSs consists of andro-sterone, epiandrosterone, etiocholanolone, DHEA, 11-keto-and lip-hydroxyandrosterone, and 11-keto- and 11(3-hydroxyetiocholanolone. DHEA and 11-oxygenated 17-KSs are produced only by the adrenal glands, whereas the others also arise from precursors (androstenedione and testosterone) elaborated by the gonads. Thus the main purpose of measuring these steroid metabolites is to assess adrenal androgen production. 

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. 

This approach to therapy appears to suffer several disadvantages. DHEA may be considered a prohormone, since it may be converted not only to the etiocholanolones, but also to testosterone or oestradiol [188]. The possible androgenic or oestrogenic activity of DHEA and DHEA sulphate [199] seems to preclude any widespread use of this steroid. The etiocholanolones are more potent and are metabolic end products (not converted to steroids with androgenic or oestrogenic activity), but appear clinically to have substantial pyrogenic activity [200],... 

Testosterone is metabohzed in the liver to androsterone and etiocholanolone (Figure 58-3), which are biologically inactive. Dihydrotestosterone is metabolized to androsterone, androstane-dione, and androstanediol. 

Fig. 11.6.3. HPLC separation of androgens. Chromatographic conditions column, two Partisil 5 columns in series (300 X 4.6 mm I.D.) mobile phase, dichloromethane-acetomtrile-2-propanol (179 20 1) flow rate, 0.4 ml/min temperature, ambient detection, UV at 254 nm and 280 nm. Peaks I, androstanedione, II, etiocholanedione III, androstenedione IV, epietiocholanolone V, dehydroepi-androsterone VI, epiandrosterone VII, androsterone, VIII, androstadienedione IX, testosterone, X, etiocholanolone XI, epitestosterone. Reproduced from Hunter et al.

The first step in the catabolism of testosterone according to Fig. 10 should be the oxidation of the 17/8-hydroxyl group to the ketone to form A -androstene-3,17-dione. Although this substance has been found in the urine of a man with adrenal hyperplasia, normally the turnover of this compound must be very rapid, since it is not present in normal urine and is not found even after the administration of large amounts of testosterone. However, the administration of isotopic, as well as nonisotopic, A -androstene-3,17-dione gave rise to the same metabolites (androsterone, XLVIII, and etiocholanolone, XLIX) as testosterone therefore, A -androstene-3,17-dione could be an intermediate in the biochemical transformation of the testicular hormone. 

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. 

Figure 3.6 Structures of selected steroidal compounds testosterone (1), 5a-dihydrotestosterone (2), androsterone (3),etiocholanolone (4), 1-dehydrotestosterone (5), androsta, 6-dien-17p-ol-3-one (6), and 17a-methylandrosta-4,9(ll)-dien-17P-ol-3-one (7).

The phase-I-metabolism of testosterone leads primarily to 5a-androstan-17P-ol-3-one (dihydrotestosterone), 5a-androstan-3a-ol-17-one (androsterone), and 5P-androstan-3a-ol-17-one (etiocholanolone) (Fig. 3.6,2-4, respectively), which represent important parameters of the so-called urinary steroid profile in sports drug testing (see Chapter 6). 

Figure 6.4 Extracted ion chromatograms of a GC-MS analysis of a qnaUty control sample containing, among others, 6 analytes ([a] desoxymethyltestosterone 7.90min [b] 19-norandrosterone 8.98 min [c] 18-nor-17,17-dimethyl-5P-androsta-l,13-dien-3a-ol 9.27min [d] l-methylene-5a-androstan-3a-ol-17-one 11.70min [e] 4-chloro-androst-4-en-3a-ol-17-one 13.88 min and [f] 3 OH-stanozolol 18.82 mm) plus the internal standards H4-etiocholanolone ([g], 10.63min) and Hs-testosterone ([h], 13.18min).

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