Metabolites of testosterone

C. In adolescent males, testicular testosterone production dramatically rises from prepuberal levels and then declines into adulthood. However, with advancing adulthood there is a drop in the metabolic clearance rate of testosterone, increasing the length of time that testosterone remains in the serum. Evidence of a relatively constant level of serum testosterone is seen in the relative constant levels of urinary 17-ketosteroids, a metabolite of testosterone, from the second to the fifth decade of life. 

Figure 3.19. Comparison of S/N for glucuronide metabolite of testosterone detected using different IDA survey scans.

The formation of metabolites of testosterone in different target organs... 

In other species, especially the Gottingen miniature pig, Booth established that androgens promote the abundant appearance of distinctive metabolites of testosterone, often exceeding 2 mmol/g wet weight [23]. The primary products are odorous steroids of the unusual 16a-androstene series, especially 3a-androstenol, 5a-... 

The reaction mixture contained 0.05 M Hepes-Na buffer (pH 7.4), MgCl2, microsomes, and 1 mM testosterone. The reaction was initiated by the addition of the NADPH-generating solution, incubated for 10 minutes at 37°C, and terminated (after addition of the internal standard corticosterone in methanol) with dichlormethane. The dichlormethane extract was dried and analyzed by HPLC. A representative chromatogram of the metabolites of testosterone is shown in Figure 9.128 and the rates of formation of the different metabolites are shown in Figure 9.129. 

Figure 9.128 Typical chromatogram of the metabolites of testosterone formed by 1.0 mg of liver microsomal protein in 1.0 mL of reaction mixture incubated for 10 minutes at 37°C with (upper trace) and without (lower trace) a source of NADPH. (From van der Hoeven, 1984.)...

Disposition in the Body. Androsterone is a naturally occurring androgen which may be isolated from male urine. It is a major metabolite of testosterone. 

Metabolites of testosterone. Seminal vesicles [8] Capon s comb [8] Ventral prostate... 

The 17-KSs are metabolites of precursors secreted by the adrenal glands, the testes, and to some extent the ovaries. In men, approximately one third of the total urinary 17-KSs represent metabolites of testosterone secreted by the testes, whereas most of the remaining two thirds are derived from the steroids produced by the adrenal glands. In women, who normally excrete smaller quantities than men, the total 17-KS concentrations are derived almost exclusively from the adrenal glands. 

Genistein and daidzein directly affect testosterone metabolism, reducing the toxic metabolites of testosterone. Genistein, an isoflavone, also seems to slow or prevent the metastasis of invasive cancer cells. It is believed to work by preventing the formation of new blood vessels to cancerous tumors. Histoculture studies of genistein have shown that this phytochemical reduces the growth of prostatic cancer tissue. 

The first testicular hormone isolated was androsterone, a metabolite of testosterone. This also was achieved by Butenandt starting with an extract from 15,000 liters of urine supplied by Schering from which he obtained only 15 mg of pure crystals. Four years later, Laquer isolated 10 mg of the primary male sex hormone, testosterone, from 100 kg of steer testis. In all cases on this table the key to isolation was the quantitative bioassay as listed. 

Nagata, K., D.J. Liberato, J.R. Gillette, and H.A. Sasame (1986). An unusual metabolite of testosterone 17P-hydroxy-4,6-androstadiene-3-one. Drug Metab. Dispos. 14, 559-565. 

An example of the use of normal phase chromatography to resolve a mixture of androgens is shown in Fig. 11.6.3. Resolution of the epimers of the monohydroxy metabolites of testosterone and androstanedione has been achieved using a mobile phase of hexane-tetrahydrofuran-2-propanol (80 15 5) with a silica stationary phase (Kawalek et al., 1981). 

Irons-Testosterone, as metabolite of testosterone, X, 258 Testosterone propionate, cortisone and, IX, 274 effect on retention of chloride, VI, 313 of sodium, VI, 313 Tetraethylammonium bromide, effect in hypertensive toxemia, X, 171... 

Men also have chemical stimulants. [14] Prelog and Ruzicka resolved the structure of 5a-androst- 16-en-3-one, the sex pheromone ofthe boar Sus scrofa domestica), [15] and, as it became clear later, also of men. [16] It is a metabolite of testosterone and its odour was described as a scent of receptacles , which had been used over a longer period to store urine. In waiting rooms, women preferred to sit rather on androstenone-impregnated chairs than on those which were untreated. Also, photographs of men, animals and houses primed with traces of 5a-androst- 16-en-3-one were considered more warm and friendlythan those which lacked the boar pheromone. 

More recently it was foundthat also androsta-4,16-dien-3-one, a metabolite of testosterone as well, has strong pheromone-like activities in humans. It affects significantly the mood of heterosexual women andhomosexual men, but it does not alter behavior overtly, although it may have more subtle effects on attention. Androstadienone is commonly sold in male fragrances, in order to increase sexual attraction. [17]... 

FIGURE 16.5 Metabolites of testosterone in Japanese quail show the resolution of LC-AMS used in defining the optimal metabolite for developing a field enzyme-linked immunosorbent assay (ELISA) test. Fractional resolution is shown for 8 Gaussian-fitted peaks. Two unresolved peaks have dashed Gaussian fits that predict a 2.6-min separation for a resolution of 0.93. 

No direct metabolite of testosterone measurable, not detectable via gas chromatographic urine profile. Sodium intake 100-200 meq/d recumbent (m) upright (j) sodium intake 10 meq/d recumbent 333-999 upright 472-3800. 

No direct metabolite of testosterone measurable, not detectable via gas chromatographic urine profile. 

A separation in the metabolic route occurs on the reduction of the double bond of A -androstene-3,17-dione (LV), affording two saturated diketones isomeric at Cs. These are rings A/B trans, androstane-3,17-dione (LX), and rings A/B cis, etiocholane-3,17-dione (LXI). Both of these diketones have been isolated from urine. " That these two diketones are true metabolites of testosterone has been shown by the isolation of the tagged substances after injection of deuterium-labeled hormone. Once the metabolic course has diverged upon the reduction of the a, unsaturated ketone to the isomeric diketones, there is no crossing over from one branch of the pathway to the other. Thus, after the administration of either deuterium-labeled or nonisotopic androstane-3,17-dione (LX), only... 

---