Androstenedione testosterone metabolite

The main excretory metabohtes of androstenedione, testosterone, and DHEA are shown in Figure 53-5. Except for epitestosterone, these catabolites constitute a group of steroids known as 17-ketosteroids (17-KSs). These metabolites are excreted primarily in the urine (>90%), with approximately half as 17-KSs, and half as diols, triols, conjugates, and other polar compounds." ... 

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... 

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-... 

Figure 9.129 Amount of hydroxylated reaction product formed by 0.75 mg of hepatic microsomal protein in 1.0 mL of reaction mixture incubated at 37°C for different lengths of time. 2a, 6jQ, 7a, and 16a-OHT are the hydroxylated metabolites of testosterone A is androstenedione. (From van der Hoeven, 1984.)...

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]. 

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. 

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. 

Occurrence other than in man The spectrum of A. in vertebrates is, in principle, qualitatively the same as that in humans although there may be quantitative differences and differences with regard to biosynthetic and metabolic details. A. have also occasionally been isolated from plants as metabolites of steroidal secondary substances, e.g., testosterone and androstenedione from pollen of Scottish pine Pinus sylvestris (Pin-aceae) and rubrosterone (2/3,3/S,14a-trihydroxy-5)8-androst-7-ene-6,17-dione), a biological degradation product of an ecdysteroid from Achyranthes rubro-fusca (Amaranthaceae). 

Testosterone and six cell tnicrosome metabolites (6j8-, 16a-, 16, 7a-, 2a-hydro-xytestosterone, and androstenedione) were well resolved and eluted in <35 min on a 40°C Cig column (A = 242nm) using a 50/38.5/11.5 water (0.1 mM Na2HP04 at pH 6)/methanol/acetonitrile mobile phase [529]. The authors make special note that the use of THF is to be avoided due to chances of its reactmg with the analytes. Linear ranges of 280-4600 ng/mL for metabolites and 20-40 pg/mL for testosterone were reported. 

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