Androstenedione 19-hydroxylation

In men, approximately 8 mg of testosterone is produced daily. About 95% is produced by the Leydig cells and only 5% by the adrenals. The testis also secretes small amounts of another potent androgen, dihydrotestosterone, as well as androstenedione and dehydroepiandrosterone, which are weak androgens. Pregnenolone and progesterone and their 17-hydroxylated derivatives are also released in small amounts. Plasma levels of testosterone in males are about 0.6 mcg/dL after puberty and appear to decline after age 50. Testosterone is also present in the plasma of women in concentrations of approximately 0.03 mcg/dL and is derived in approximately equal parts from the ovaries and adrenals and by the peripheral conversion of other hormones. 

Several sex-dependent differences have been observed in the action of cytochrome P450 isoenzymes on steroid hormones.290 2903 Thus, androstenedione is hydroxylated by rat liver enzymes specific for the 60, 7a, 16a, and 160 positions.291 Of these the 16 hydroxylase is synthesized only in males, and synthesis of the 6 hydroxylase is also largely suppressed in females. 

The pL (L = H or D) dependence of the solvent DIEs associated with progesterone 493 oxidation to 17a-hydroxyprogesterone 494 and 17-0-acetyltestosterone 495 and 17a-hydroxyprogesterone oxidation to androstenedione 496 has been determined in microcosms from pig testes580 (equation 290). The initial rate of oxidation of 493 to 494 has been associated with the pL-independent inverse solvent isotope effect (SIE) (fce/ D = 0.75 — 0.95 in 30% DOD) while the oxidation of 495 has been associated with the pL-independent positive SIE in 30% DOD (ku/ku of about 2), DOD inhibited the formation of 496 from 444 in noncompetitive in pL-dependent manner. Androgens are synthesized from progesterone in a two-step reaction involving the 17a-hydroxylation... 

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... 

Fig. 12. Classical pathways for oestrogen biosynthesis, indicating 19-hydroxylation and 19-oxidation of 4-androstenedione and testosterone, followed by C-10.19 bond cleavage catalysed by a presumed C-10.19-lyase.

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.)...

The answer is d. (Murray, pp 505-626. Scriver, pp 4029-4240. Sack, pp 121-138. Wilson, pp 287-320.) Both cortisol and aldosterone contain C-21-hydroxyl groups. Both are also derived from progesterone in the adrenal cortex. In contrast, the sex hormones are synthesized in the ovaries and testicular interstitial cells. In the synthesis of sex hormones, progesterone is converted to 17a-hydroxyprogesterone and then androstenedione, which may either become estrone or testosterone. Testosterone gives rise to estradiol in the ovaries. In the corpus luteum, progesterone is produced. 

M2. Mancuso, S., Benagiano, G., Dell Acqua, S., Shapiro, M., Wiquist, N., and Diczfalusy, E., Aromatization and hydroxylation products formed by previable fetuses perfused with androstenedione and testosterone. Acta Endocrinol. 67, 208-227 (1968). 

Steroids are good substrates for microbiological reductions however, the reductions often lead to unwanted side reactions of desired transformations such as hydroxylations. The first report in 1937 291 dealt with baker s yeast reduction of the 3- and 17-groups and led to the synthesis of estradiol from estrone and testosterone from androstenedione. 

Flavonoids are 2-phenyl-l-benzopyran-4-one derivatives which are widely distributed throughout the plant kingdom. Some synthetic flavonoids, notably the 7,8-benzoflavones (a-naphthoflavones (15), lUPAC name 2-arylnaphtho-[ 1,2-l>]pyran-4-ones), chrysin and apigenin, have been shown to act as potent competitive inhibitors of human placental aromatase [135, 136], In this system, 7,8-benzoflavone and chrysin have IC50 values of 70 and 500 nM respectively (androstenedione as substrate). Hydroxylated metabolites of... 

The principal androgenic or male sex hormone is testosterone formed from pregnenolone through removal of the side chain at C-17. The first step in the conversion is 17a-hydroxylation by a cytochrome P450 which may also mediate the further oxidative cleavage to A -androstenedione (Fig. 22-11). Reduction of the... 

A role of sodium chlorite in supporting cytochrome P450-catalysed steroid hydroxylation was studied using microsomal fractions prepared from the livers of male Sprague-Dawley rats. In the presence of 4 mmol sodium chlorite/l, the generation of hydroxylated androstenedione metabolites during a 10-min incubation period was 67% of that in the presence of 1 mmol of reduced nicotinamide adenine dinucleotide phosphate (NADPH) per litre (Hrycay et al., 1975). 

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