Inhibition of the conversion of cholesterol to pregnenolone in bovine adrenocortical preparations

Article abstract of DOI:10.1016/0039-128X(76)90057-X

The inhibition of the conversion of [4 ¹⁴C] cholesterol to [4 ¹⁴C]pregnenolone by a number of steroids has been studied in bovine adrenocortical mitochondrial acetone dried preparations. At equimolar substrate and inhibitor concentrations (3.3 μM) the most potent inhibitors were cholesterol derivatives containing a nitrogen function at C 22, followed by derivatives containing oxygen function at C 22 or C 20 or both. The presence of a hydroxyl group at C 17 or the replacement of the 3β hydroxyl group by fluorine reduced the inhibitory efficacy. In the presence of inhibitors that were also relatively good substrates of the cholesterol side chain cleavage system, such as some cholesterol derivatives hydroxylated in the side chain, the rate of [4 ¹⁴C]pregnenolone formation increased with time as the inhibitor was consumed. (20S) 20,21 Dihydroxycholesterol exerted such an effect on the kinetics of [4 ¹⁴C]pregnenolone formation, and yielded 21 hydroxypregnenolone which was identified by gas chromatography mass spectrometry. The synthesis of (20R) 22 ketocholesterol, of (20R, 22R) 22 hydroxycholesterol, (20R, 22S) hydroxycholesterol, and of (20S) desmosterol is described.