In vitro studies of the adrenal metabolism of halogenated side-chain analogues of cholesterol.

The cholesterol side-chain cleavage enzyme system of rat adrenal mitochondria and rat adrenocortical carcinoma cells was found to metabolize three halogenated side-chain cholesterol analogues to pregnenolone. The analogues were 26-bromocholesterol, 26-nor-25(RS)-bromocholesterol and 26-iodocholesterol. The addition of Ca2+ to rat adrenal mitochondria did not produce an increase in the rate of metabolism of the halogenated sterol to pregnenolone. The brominated sterols suppressed the de novo sterol biosynthesis of rat adrenocortical carcinoma cells. The experimental findings are supportive of the notion that a halogen atom at such a position in a sterol is analogous to a hydroxyl group but unlike a proton. ACTH, therefore, may not be a requirement for the uptake and utilization of such sterols. The halogenated sterols may have a use as probes in the study of sterol transfer into and within cells.