Hydroxy androstenedione

Ketoetiocholanolone 11/3-Hydroxy androsterone 1 l/S-Hydroxyetiocholanolone 0.4-2.0) 0.2-1.0> 0.1-0.5j Cortisol, 11/3-hydroxy-androstenedione... 

An issue with the ferric peroxide mechanism is that the substrate is in the (hydrated) gew-diol form following the second reaction (Fig. 9.28). However, the proposed ferric peroxide mechanism involves a nucleophilic attack (Fe " 02 ) on the carbonyl (aldehyde). Thus, the gew-diol must be dehydrated before this step can run. The rate of dehydration has been estimated at > 0.5 s (in the absence of P450 19A1 using 0 exchange methods [2295], which is faster than the (8 min ) for going from 19-hydroxy androstenedione to estrone [220]. The reaction could occur with the aldehyde or the ge/w-diol, the latter of... 

Rauh M, Groschl M, Rascher W, Dorr HG (2006) Automated, fast and sensitive quantification of 17 alpha-hydroxy-progesterone, androstenedione and testosterone by tandem mass spectrometry with on-line extraction. Steroids 71 450-458... 

Fig. 2. Biosynthesis of testosterone (a) Pregnenolone (b) 17-hydroxy pregneno-line (c) dehydrois-oandrosterone (d) progesterone (e) 17-hydroxypro ges terone If androstenedione (g) testosterone...

Formestane (Figure 5.138), the 4-hydroxy derivative of androstenedione, represents the first steroid aromatase inhibitor to be used clinically. It reduces the synthesis of oestrogens and is of value in treating advanced breast cancer in post-menopausal patients. 

The conversion of androstenedione to estrone is catalyzed by aromatase. Inhibition of aromatase (human estrogen synthetase) by several naturally occurring flavonoids, including quercetin, chrysin, and apigenin, has been described. The synthetic flavone 7,8-benzoflavone was most active. Aromatization of androstenedione was affected by several flavonoids, of which 7-hydroxy-flavone and 7,4-dihydroxyflavone were the most potent. 

There are also distinct possibilities that at least two forms of the adrenal mitochondrial 11/3-hydroxylase may exist, one in the ZG, involved in the conversion of DOC into aldosterone (Fig. 6) and another in the ZF/ZR, concerned with the conversion of DOC to cortisol and 4-androstenedione to ll/3-hydroxy-4-androstenedione. An alternative possibility is that several cyts P-450Uj3 may exist, which catalyse the 11/3-hydroxylation of DOC, 11-deoxycortisol and 4-androstenedione [60,61]. To make... 

The first step in the conversion of 4-androstenedione to oestrone is the hydrox-ylation at C-19, a reaction associated with the ER and which requires NADPH and 02. It was thought earlier that the 19-hydroxy derivative was then converted to the 19-aldehyde, which gave rise to oestrone or oestradiol-17/3 (from 4-androstenedi-one or testosterone, respectively) as rupture of the bond between C-10 and the angular methyl group at C-19 occurred through C-10,19-lyase action (Fig. 12). More recent studies [42,52] have resulted in the proposal of at least three mechanisms, which all involve a second stereospecific hydroxylation at C-19 (requiring a second... 

There is evidence [52] that there are at least two forms of cyt P-450 involved with aromatization. Likewise, there is evidence for different aromatases in human placenta which catalyse the production of oestrone and oestriol from 4-androstenedi-one and 16a-hydroxytestosterone, respectively. Each enzyme system has been subfractionated into its own cyt P-450 and cyt P-450 reductase [107]. This has been supported recently by Purohit and Oakey [108], who measured aromatase activity for 16a-hydroxy-4-androstenedione and 4-androstenedione in the presence or absence of the other substrate. 4-Androstenedione competitively inhibited aromatization of the 16a-hydroxy derivative, with apparent K, essentially the same as its apparent Km, suggesting that both substrates bind and are aromatized independently of each other. The 16a-hydroxy derivative competitively inhibited the aromatization of 4-androstenedione, thus presumably lowering the affinity of the aromatase for the latter. 

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 oxidation of a secondary alcoholic group in the presence of primary alcoholic groups by Acetobacter suboxydans converts adonit into adonose [1041]. The treatment of androstenediol and dehydroandrosterone with yeast yields A -androstenedione [1088]. Steroidal hydroxy ketones are dehydrogenated to dicarbonyl compound with CorynebacteriUlh simplex [1056] (see equations 446 and 447). Examples of oxidations of secondary alcohols to ketones are shown in equations 265-268. 

Estrogens. The biosynthetic relationship of the ovarian female sex hormones to androstenedione (their precursor), to cholesterol, and to each other is outlined in Figure 14-6. Estrone [3-hydroxy-l,3,5(10)-estratriene-17-one] was the first sex hormone to be isolated (Doisy et al., 1930 Butenand, 1930). Estradiol, which has been established as the true female sex hormone, is about 10 times more potent than estrone. It was not isolated for five years and took the extraction of 4 tons of sow ovaries to produce a little more than 10 mg of the hormone. Estrone was initially isolated from human pregnancy urine. 

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