17«-Hydroxy progesterone, hydroxylation

Aldosterone production is initiated by 21-hydroxylation of pregnenolone in the adrenal glomerulosa, where there is no 17-hydroxylase activity. The product of hydroxylation of pregnenolone by P450c21 is 21-hydroxy-progesterone, also known as deoxycorticosterone (DOC). The quantity of aldosterone produced by the adrenal is only 1% of that of cortisol for this reason, not all patients with classic P450c21 deficiency manifest with salt wasting. 

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-... 

The 17-ketosteroids increased in the urine include dehydroepiandrosterone, androsterone, etiocholano-lone, and 11-hydroxy- and 11-oxy-derivatives. Thus, it would appear that as a result of the block in 21-hydroxylation, the rate of conversion of 17-hydroxy-progesterone to carbon 19 compounds is increased. These results indicated that the adrenals of these patients are capable of 11-hydroxylations in spite of the fact that 21-hydroxylation does not take place. As a result of 11-hydroxylation, 11-ketosteroids, and especially 11-ketopregnaetriol, are excreted in excessive amounts in the urine of patients with adrenogenital syndrome. Thus, 17-hydroxyprogesterone is direct-... 

In the biosynthetic steps from progesterone to the adrenal cortical hormones are the very important 21-, lljS-, and 18-hydroxylations. The major pathway of synthesis is illustrated in Fig. 18. The properties of the enzyme, 17a-hydroxylase, which catalyzes the initial step in the formation of cortisol, have been described in a previous section, IV.B, of this manuscript. 21-Hydroxylation of progesterone or 17a-hydroxy-progesterone precedes 1 lj8-hydroxylation resulting in the eventual formation of the glucocorticoids, corticosterone, and cortisol respectively. The further conversion of corticosterone by 18-hydroxylation and sub-... 

The most important microorganism for the introduction of a hydroxy group in the 12/J-position of steroids is the pink fungus, Calonectria decora. Nevertheless, 12-hydroxylation is accompanied by the introduction of a second hydroxy group in the 15x-position. In the case of progesterone (1), a 77 % yield of 12/ .15a-dihydroxyprogesterone (2) has been reported234- 2 3S. 

Microbial hydroxylation of 9/f,10a-progesterone (3) with Colletotrichum gloeosporioides gives the 15 -hydroxy derivative 4 in 29% yield257. 

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