11 -Deoxycorticosterone, from progesterone

Hydroxylation has been studied only in terms of aldosterone biosynthesis. A detailed investigation of precursors of this mineralocorticoid has been conducted and is described in full by Ayres et al. (1960). Corticosterone is transformed somewhat more rapidly than deoxycorticosterone or progesterone (Fig. 18). 18-Hydroxydeoxycorticosterone has been isolated from incubations of rat adrenal sections in the presence of TPNH and oxygen (Peron, 1961). Its further conversion (11/3-hydroxylation) to aldosterone, however, has not been reported. 

Cholestenone (derived from unreacted cholesterol) and progesterone were separated from deoxycorticosterone acetate (internal standard) by normal phase chromatography on a TSK-gel silica 150 column (4 mm x 250 mm)... 

Figure 9.85 Normal phase HPLC profiles of the reaction product of the cholesterol side chain cleavage system. Peaks were identified on the basis of their retention times. (i4) Without cholesterol oxidase treatment. Cholesterol (100 nmol) was incubated with cytochrome P450scc (70 pmol) in the presence of adrenodoxin, adrenodoxin reductase, and an NADPH-generating system. Monitoring was at 214 nm. Peaks 1, cholesterol 2, pregnenolone 3, deoxycorticosterone acetate (internal standard) (B) The reaction mixture of (A) was further incubated with cholesterol oxidase at 37°C for 10 minutes. Monitoring was at 240 nm. Peaks 1, cholestenone 2, progesterone 3, deoxycorticosterone acetate (internal standard). (From Sugano et al., 1989.)...

Progesterone is synthesized from either cholesterol or alkylated plant sterols by a pathway similar to that in animals. Hydroxylation at C-20 and C-22 is a prerequisite for removal of the C-6 residue of the side chain (A, B, C, Fig. 16). The product pregnenolone is then reduced to progesterone (D, Fig. 16). Traces of oestrone, testosterone, deoxycorticosterone and closely related compounds have been found in plants but nothing is known of their biosynthesis. 

Fig. 11.6.2. HPLC separation of steroid standards. Chromatographic conditions column, Hypersil ODS (150x4.6 mm O.D.) mobile phase, concave gradient (dashed line) of methanol-water (40-60% methanol) flow rate, 1 ml/min temperature, 45 °C detection, UV at 240 nm. Peaks A, 11-dehydrocorticosterone AD, androstenedione ALDO, aldosterone, B, corticosterone DHP, dihydroprogesterone DOC, 11-deoxycorticosterone E, cortisone F, cortisol G, adrenosterone, P, progesterone S, 11-deoxycortisol T, testosterone. Reproduced from O Hare and Nice (1982), with...

Permeabihty coefficients for black rat snake were taken directly from Table II for ibuprofen, naproxen, ketoprofen, deoxycorticosterone, 1 la-hydroxyprogesterone, corticosterone, and hydrocortisone. Permeabihty coefficients for indomethacin and progesterone were not inclnded because they were not measured from aqueous solurion. Permeability coefficients for the parabens were not included because they are idenrical to those reported by Itoh, Xia, et al. (1990). 

HvdroxYlation. The first reports of 15/3-hydroxylation were from Fried and associ ites i AiPhycomycesblakesleeanus on progesterone (F-285 - F-288) and from Meystre, Vischer, and Wettstein with Lenzites abietina on deoxycorticosterone (M-585, W-1087). The 15/3-hydroxylation of Compound S goes especially well with Bacillus megaterium (H-382). 

Ap-63 Rahim, M. A., and Sih, C. J., J. Biol. Chem. 241. 3615 (1966). In vitro studies of oxygenase and esterase from Cylindrocarpon radicicola. Degradation of progesterone, 17a-hydroxyprogesterone, 16-dehydroprogesterone, deoxycorticosterone, and 16a, 17a-oxidoprogesterone to C-19 steroids. 

There is little question that the site of steroid conversions is intracellular. Complete removal of follicle cells which remain adherent to oocytes after manual dissection from their follicles does not alter chromatographic profiles, either quantitatively or qualitatively. Likewise, the profiles obtained from oocytes injected with radioactive progesterone were essentially identical to those obtained by incubation of oocytes with exogenous hormone. Thus, the observations reveal a heretofore unsuspected capability of oocytes to participate in steroid metabolism. This is not restricted to Bana pipiens, but also has been observed in Xenopus laevis and Rana catesbiana. Likewise, both exogenous deoxycorticosterone and estradiol are metabolized by isolated oocytes, giving rise to different kinds of metabolites than obtained with progesterone (Reynhout and Smith, 1973). 

P450 21A2 is the enzyme involved in the 21-hy-droxylation of progesterone and 17-hydroxy-progesterone, yielding deoxycorticosterone and 11-deoxycortisol from the two substrates, respectively (Fig. 9.12). The 21-hydroxylation reaction is an important step in the synthesis of glucocorticoids and mineralocorticoids, and de-... 

Pathways not involving 17 a-hydroxylation are not altered, and there is no decrease in deoxycorticosterone, which derives from the 21-hydroxylation of progesterone, and corticosterone, which is formed by the 11 j8-hydroxylation of deoxycorticosterone. 

From perfusion data, it is known that the midterm fetus converts progesterone to 20a-dihydroprogcsterone, 16a-hydroxyprogesterone, cortisol, and corticosterone (Solomon et al., 1964 Bird et al., 1966) and to corticosterone sulfate and deoxycorticosterone sulfate (Bird et al., 1965). Most of these reactions take place principally in the adrenal tissue (see Section III, D, 2 b, 3 b, and E, 2 b). 

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