Metabolism of testosterone

Ronis, M.J.J. and Mason, Z. (1996). The metabolism of testosterone by the periwinkle in vitro and in vivo effects of TBT. Marine Environmental Research 42, 161-166. 

Buur A, N Mprk. (1992). Metabolism of testosterone during in vitro transport across Caco-2 cell monolayers Evidence for beta-hydroxysteroid dehydrogenase activity in differentiated Caco-2 cells. Pharm Res 9 1290-1294. 

Researchers discovered that MPA also had effects on men. When injected into a man, MPA accelerates the metabolism of testosterone while also suppressing its production. The result is a reduction of up to 75 percent in the amount of testosterone in the man s body, thus lowering the intensity of inappropriate sexual cravings and the frequency of unacceptable erotic pre-... 

Grant JK, Mingnell J, Taylor P, Weiss M. (1971) A possible role of zinc in the metabolism of testosterone by the prostate gland. Biochem J125 21P... 

In all species, metabolism of testosterone leads to its biological deactivation. In sheep and cattle, this biological deactivation leads mainly to formation of epitestosterone, whereas in nonruminants it leads to androsterone, etiocholano-lone, and dehydroepiandrosterone (7-9). Residues of endogenous testosterone are usually highest in the kidneys of animals such as heifers witli a low testosterone production rate, and highest in fat of animals such as bulls, with a high production rate. 

Deuterium isotope effect study of the metabolism of testosterone by CYP2C11... 

Since the distinctive metabolism of testosterone provides the most plausible explanation of the diversity of androgenic responses, brief reference should be made to the enzymes involved. Such a summary is presented in Table 2. Crucial enzymes include microsomal and nuclear NADPH-dependent 5a-reductase, the microsomal... 

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. 

Androsterone and 5)3-androsterone, which are the major metabolites, were thought to be uniquely derived from the plasma androstenedione pool. Korenman et al. [170,388] demonstrated by the double isotope tracer method using carbon-14-labeled testosterone and tritium-labeled androstenedione that neither androsterone nor 5 -androsterone is a unique metabolite of a plasma androstenedione pool. A unique steroid metabolite has been defined by Dorfman [326] as a steroid persisting or formed during metabolism which can be related to one and only one tissue steroid. Korenman et al. obtained different tritium/carbon-14 ratios for androsterone and 5/3-androsterone, suggesting that other pathways of testosterone and androstenedione metabolism also exist. These other pathways, possibly metabolism of testosterone and androstenedione by peripheral tissue, may be responsible for the relative enrichment of either the 5a- or the 5/8-isomer of the urinary metabolites [305]. 

Figure 23-23 Metabolism of testosterone and 5 DHT (conjugates of the metabolites ate also formed ...

Depression of testicular production and increase in peripheral metabolism of testosterone, independent of hver disease ... 

In Table 2 the major metabolites of the steroid sex hormones and some important related steroids are listed. Their relationships to their precursors are in some cases controversial at present and will be discussed in the next section of this article. Suffice it to say at the moment that simple relationships between the excretion rates of some of these metabolites and the secretion rates of their precursors are not easy to establish. On the other hand, it is fair to add that some of the complexities implied by recent work on the metabolism of testosterone and andros-tenedione, and on the metabolic activity of the placenta and fetus in pregnancy should not be allowed to obscure the relative simplicity of many aspects of the metabolism of progesterone and of estrogens. 

B4. Baulieu, E. E., Lasnitzky, I., and Robel, P., Metabolism of testosterone and action of metabolites on prostate glands grown in organ culture. Nature 219, 1155-1156 (1968). 

Both acute and chronic alcohol use can lead to impotency in men. Increased blood alcohol concentrations lead to decreased sexual arousal, increased ejaculatory latency, and decreased orgasmic pleasure. Additionally, many chronic alcoholics develop testicular atrophy and decreased fertility the mechanisms are complex and likely involve altered hypothalamic function and a direct toxic effect of alcohol on Leydig cells. Testosterone levels may be depressed, but many men who are alcohol-dependent have normal testosterone and estrogen levels. Gynecomastia is associated with alcoholic liver disease and is related to increased cellular response to estrogen and to accelerated metabolism of testosterone. 

FIGURE 58-3 Metabolism of testosterone to its major active and inactive metabolites. 

U.smani, K, A Ro.se, R. L., and Hodgson. E. (2003). Inhibition and activation of the human liver microsomal and human cytochrome P430 3A4 metabolism of testosterone by deployment-related chemicals. Dru Meiah. Dispos. 31, 384-391. 

The ability of parathton to interfere with the metabolism of androgen, as well as the uptake, in male accessory organs in rats was described in the 1960s and 1970s (Kupfer, 1967 Schein and Thomas, 1976 Thomas and Schein, 1974). The oral administration of parathion (1.3-5.2 mg/kg/day) caused significant alterations in the metabolism of testosterone in mice. An early study suggested that this compound... 

Later, Nixon et al. 60S) investigated the metabolism of testosterone, pregnenolone and 5-fl// /ifl-dehydrotestosterone by human axillary corynebacteria and demonstrated that pregnenolone was metabolized to 5-fl//7/ fl-dehydroandrosterone and an unidentified compound, while testosterone was converted to 5-a// Aa-dehydrotestosterone and 11-beta-hydroxy-3-6e/a-androst-3-one. 

Dessi-Fulgheri, F., C. Lupo, G. Ciamp, M. Canonaco, and K. Larsson Exposure to Odor During Development and Hypothalamic Metabolism of Testosterone. In J. Balthazar, E. Preeve, and R. Giles eds.. Hormonal Behavior in Higher Vertebrates, p. 305-312. Berlin Springer 1982. 

Considerable study has been devoted to the enzyme systems involved in the metabolism of testosterone. In rat liver minces or slices, the enzyme... 

Krieg, M., Szalay, R., and Voigt, K. D., 1974, Binding and metabolism of testosterone and of 5o -dihydrotestosterone in bulbocavemosus/levator ani (BCLA) of male rats. In vivo and in vitro studies, /. Steroid Biochem. 5 453. 

One final area where steroids are used is as antiandrogens in the treatment of benign prostatic hyperplasia, prostate cancer and male hypersexuality. Dutasteride and finasteride (Fig. 20.34) are specific inhibitors of 5a-reductase, which is involved in the metabolism of testosterone. These two compounds are indicated for the treatment of benign prostatic hyperplasia, with finasteride also being indicated for male-pattern baldness. 

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). 

---