Cholesterol sulfate metabolism in human fetal adrenal mitochondria

The metabolism of cholesterol sulfate (5-cholesten-3 beta-ol sodium sulfate) and cholesterol to pregnenolone sulfate and pregnenolone, respectively, in human fetal adrenal mitochondria has been investigated. Cholesterol sulfate (50 microM) was converted efficiently to pregnenolone sulfate (5-pregnen-3 beta-ol-20-one sodium sulfate; 1.6 nmol min-2 mg-1 protein). Pregnenolone sulfate biosynthesis from endogenous mitochondrial precursors could not be detected. The rate of pregnenolone biosynthesis in the presence of cholesterol (50 microM) was 0.2 nmol min-1 mg-1 protein. In contrast, mitochondria obtained from the adrenal tissue of a boy and two adult men did not produce detectable amounts of pregnenolone sulfate after the addition of cholesterol sulfate (50 microM). Pregnenolone was produced efficiently by adrenal mitochondria from endogenous mitochondrial precursors and was not stimulated by the addition of cholesterol (100 microM). The results suggest that human fetal adrenal mitochondria contain a specific cholesterol sulfate desmolase and that cholesterol sulfate may be the predominant sterol substrate for the large amounts of steroid sulfates produced by this tissue. Whereas the metabolism of cholesterol to form pregnenolone was increased by the addition of 1 mM calcium ions, the metabolism of cholesterol sulfate to produce pregnenolone sulfate was not stimulated by calcium ions. This latter finding may indicate that the metabolism of cholesterol sulfate in the human fetal adrenal gland is controlled separately from the metabolism of cholesterol.