Androstenedione metabolism

Schweikert, H. U. and Wilson, J. D. (1974b). Regulation of human hair growth by steroid hormones II Androstenedione metabolism in isolated hairs. J. Clin. Endocrinol. Metab. 39,1012-1019. 

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]. 

Recently, Voogt et al. [91] have reported on the d5-pathway in steroid metabolism of Asterias rubens. These workers established the existence of the d5-pathway (Scheme 20), analogous to the pathway found in mammals this conclusion was based on the observation that radiolabeled cholesterol (1) was converted to pregnenolone (112), 17a-hydroxypregnenolone (141), and androstenediol (142). Labeled pregnenolone was converted additionally to progesterone (129). Androstenediol (142) was the main metabolite of de-hydroepiandrosterone (143), a reaction catalyzed by 17/i-hydroxysteroid dehydrogenase (17/1-HSD). The metabolic conversion of androstenedione (131) to testosterone (132) is also mediated by 17/J-HSD and is related to... 

Aminopyrine, 234 Aminotetradine, 265 2-Aminothiazole, 247 2-Aminothiazole synthesis, 126 Amisotetradine, 266 Amobarbital, 268 Amopyroquine, 342 Amoxycillin, 414 Amphetamine, 37, 70 Ampicillin, 413 Amprolium, 264 Amytriptylene, 141, 404 Anabolic effects, 169 Androgens, discovery, 155 Androstanolone, 173 Androstenedione, 158, 176 Anesthesia, parenteral, 56 Angst, 363 Anileridine, 300 Aniline, metabolism. 111 Anisindandione, 147 Anovlar , 186 Antagonists, 20, 65 Antazoline, 242 Antibodies, 41... 

Testosterone metabolism. The lipido-ste-rol extract (LSESr, Permixon) was studied in primary cultures of epithelial cells and fibroblasts separated from benign prostate hypertrophy and prostate cancer tissues. The extract inhibited the formation of the T metabolites androstenedione 5 4 and 5 a-DHT The lipophilic extracts of fruits inhibited T 5p-reductase (EC 1.3.99.5) (5(xR). For fatty acid-like 5(xR inhibition a strongly polar end-group and a molecular skeleton allowing nonpolar interactions with the enzyme were required. The result indicated that 5pR activity in prostatic tissue may be influenced by the lipid environ-... 

Aminoglutethimide [ah me no glue TETH i mide] is useful in second line therapy for the treatment of metastatic breast cancer. It inhibits the adrenal synthesis of pregnenolone from cholesterol, and the extra-adrenal aromatase reaction responsible for the synthesis of estrogen from androstenedione. Aminoglutethimide is administered orally, and is metabolized by the hepatic cytochrome P-450 system to inactive products. Because of its ability to induce this system, its own metabolism is accelerated, and interactions that increase the metabolism of dexamethasone (see p. 275), theophylline (see p. 220) and digoxin (see p. 158) can occur. Aminoglutethimide causes transient CNS depression and a maculopapular rash. 

It has been shown that hormones are not exclusive products of the glands but are also formed in metabolizing organs. These hormones, however, contrary to the classical hormones, are not secreted into the blood. It has been established that testosterone formed in the liver from androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate does not enter the blood [305,323,388]. It has also been established that secreted and metabolically produced testosterone do not have the same metabolism [169, 311]. 

The application of the twin ion technique [257] is also of importance in metabolism studies. The doubly labelled steroids [4- C+ 7-l- Ho.44]-androstenedione and [4- C + 7/3- Ho.42]-testosterone, were incubated with human placental microsomes and the resulting metabolites quantitated by counting C and identified by GC-MS [258]. The identified metabolites 17/8,19-dihydroxyandrost-4-en-3-one, 19-hydroxyandrost-4-en-3,17-dione, 17/8-hydroxy-3-oxo-androst-4-en-3-one, 3,17-dioxoandrost-4-en-19-al, oestradiol-17/3 and oestrone were easily recognisable from the double sets of relevant ions in their spectra due to the mixture of hydrogen and deuterium substitution at C-7. Hence the presence of the aromatizing enzymes in the placental preparation and the intermediates in oestrogen biosynthesis were confirmed. 

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. 

The use of androstenedione (16.3), as a metabolic precursor of testosterone, to increase athletic prowess is unproved and may lead to detrimental effects, such as elevated blood lipid levels, liver problems, and testicular atrophy.35... 

Adrenocortical steroid hormones have a vast array of biological functions. Cortisol, the primary human glucocorticoid, regulates the inflammatory response (Newton and Holden, 2007), carbohydrate and lipid metabolism, and stress response (Kassel and Herrlich, 2007). Aldosterone regulates blood pressure by modulating fluid and electrolyte balance (Brizuela et ah, 2006 Foster, 2004). In the adrenal cortex, dehydroepiandrosterone (DHEA), dehy-droepiandrosterone sulfate (DHEA-S), and androstenedione are the androgens produced (Havelock et ah, 2004 Rainey et ah, 2002). 

The 19-azido (93) and 19-methylthio (94) 4-androstene-3,17-diones have been found to be potent competitive reversible inhibitors (Kj = 5 nM and /fj = 1 nM respectively, for (androstenedione) = 25 nM). The same workers also discovered that 19-methanesulphonylthioandrostene-3,17-dione (95) inactivates AR in the presence of NADPH and Oj, although no kinetic or inhibitory data were presented [213]. The interaction of (94) with the active site was found to differ from that of (95) in that the latter displaces the substrate steroid from its binding site and on metabolism deactivates the enzyme, whereas (94) interacts with the substrate binding site but also with the haem-iron complex via a postulated coordinate bond. The differences in binding were deduced by examination of the ultraviolet spectral changes induced by the addition of the two inhibitors to the AR enzyme preparation. 

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