Cholesterol biosynthesis in human fetal liver and adrenal

Abstract

Hepatic and adrenal cholesterol biosynthesis were investigated in the human fetus in vitro by measuring the incorporation of acetate-2-14C into cholesterol by slices of liver and adrenals from the same fetus. To differentiate neutral lipids from cholesterol biosynthesis, the radioactivity was measured in the nonsaponifiable neutral lipid fraction and in cholesterol isolated and purified as its crystalline 5,6-dibromo-derivative. Expressed in mμmoles acetate incorporated/hr/g tissue into neutral lipids (n.l.) and cholesterol, the values were: fetus I (11 wk. old), liver (84.4), 49.1; adrenals (48.8), 9.3; fetus II (14 wk. old), liver (91.3), 47.3; adrenals (15.6), 5.5, respectively. Liver and adrenal cholesterogenesis was inhibited by a specific inhibitor [trans-1,4-bis (2-chlorobenzylaminomethyl)cyclohexane dihydrochloride = AY-9944] of 7-dehydrocholesterol Δ7-reductase. This finding provided (indirect) evidence that 7-dehydrocholesterol is an obligatory intermediate in the biosynthesis of cholesterol in both of these organs. The percent incorporation of acetate into cholesterol in the human fetal liver was greater than that in any other tissue previously reported.