Effect of Androgens on Steroid C-21 Hydroxylation^*

Abstract

C-21 hydroxylation of progesterone, 17 -hydroxyprogesterone, pregnenolone, and 17a-hydroxypregnenolone was studied using the microsomal fraction of bovine adrenal cortex as the source of "steroid C-21 hydroxylase." 4-Androstene-3,17-dione, testosterone, and dehydroepiandrosterone do not ihhibit C-21 hydroxylation of progesterone and 17a-hydroxyprogesterone in contrast to the inhibitory action of the adrenal androgens on 11 d-hydroxylation step in corticosteroid biosynthesis. However, C-21 hydroxylation of pregnenolone and 17a-hydroxypregnenolone was markedly inhibited by 4-androstene-3,17-dione, testosterone, and dehydroepiandrosterone. This is of particular significance since 17 -hydroxypregnenolone and not 17 -hydroxyprogesterone has been suggested to be the primary precursor of cortisol, and intraglandular modulation of steroid biosynthesis at least in part correlates certain clinical findings. Effect of pharmacological inhibitors 1,2-bis-(3-pyridyl-2-methyl-l-propanone), 3-(6-chloro-3-methyl-2-indenyl)pyridine, 3-(1,2,3,4-tetrahydro-l-oxo-2-naphthyl)pyridine, and the 7-chloro derivative of 3-(l,2,3,4-tetrahydro-l-oxo-2-naphthyl)pyridine on steroid C-21 hydroxylation has also been reported.

Testicular Sterols. IV. End-Product Steroid Inhibition of Lanosterol Demethylation*

“…The concentration of protein was lower in homogenates of testicular tissue (60-85 mg/flask) than in liver (123-184 mg/flask). the rates of both hydroxylation (Sharma et al, 1963;Sharma and Dorfman, 1964;Koritz and Hall, 1964) and dehydrogenation (Kowal et al, 1964).…”

“…Demethylation is initiated by microsomal-catalyzed hydroxylation of the methyl groups (Olson et al, 1957). Similar hydroxylations of steroidal 11-C, 21-C, and 20-C are inhibited by androstenedione (androst-4-ene-3,17-dione), testosterone (17/3-hydroxyandrost-4-en-3-one), or pregnenolone (3fl-hydroxypregn-5-en-20-one) (Sharma et al, 1963;Sharma and Dorfman, 1964;Ichii et al, 1963;Koritz and Hall, 1964). The demethylation of lanosterol proceeds by dehydrogenation of the hydroxymethyl group to the aldehyde, acid, and cleavage as C02 (Olson et al, 1957).…”

Enzymatic Mechanisms in Steroid Biochemistry

“…The pH optimum for hydroxylation of deoxycortico sterone has a sharp maximum near 7.5. More recent studies (112,113) on the l1,6-hydroxylation of deoxycorticosterone by such lyophilized enzyme prepa rations have established that the reaction is inhibited competitively by �4-androstene-3, 17 -dione, testosterone, and 3,6-hydroxy-�5-androsten-17 -one (and its sulfate), whereas 11,6-hydroxy-�4-androstene-3,17-dione, and certain other steroids were inactive. It seems likely that the inhibitory effect of the C19 steroids is due to their participation as substrates in the hydroxylation reaction.…”

Studies on Aldosterone Biosynthesis in Vitro*

“…In contrast to the inhibitory action of testosterone, androst-4-ene-3,17-dione, and DEA on 113 and C-21 hydroxylation (Sharma et al, 1963;Sharma and Dorfman, 1964), these androgens had no effect on C-18 hydroxylation of corticosterone as well as on the conversion of 18-OH-corticosterone into 18-OH-11-dehydrocorticosterone. Neither estrone nor 173-estradiol exerted any inhibitory effect on aldosterone biosynthesis (Table V).…”