Cholesterol synthesis in human fetal tissues

Large quantities of cholesterol are required to maintain optimal rates of steroidogenesis by the human fetal adrenal gland. Since the fetus itself is believed to be the principal source of the cholesterol used by the fetal adrenal, accurate measurements of cholesterol formed de novo in various fetal tissues is of signal importance in understanding the regulation of cholesterol metabolism in the fetus and, more specifically, the regulation of steroidogenesis in the fetal adrenal. In the present investigation we determined the rates of cholesterol formed de novo in short term incubations of fetal tissues obtained from human abortuses. The rates of cholesterol synthesis were determined by measuring the incorporation of tritium from [³H]water into cholesterol. The highest rates of cholesterol synthesis were found in adrenal and liver tissues (mean ± SE, 46 ± 2 and 32 ± 2 ng atoms tritium incorporated mg protein⁻¹ h⁻¹, respectively), whereas intermediate rates were found in testicular tissue (21 ± 3 ng atoms tritium incorporated mg⁻¹ h⁻¹), and lower rates (<6 ng atoms tritium incorporated mg⁻¹ h⁻¹) were seen in all other tissues studied. Small but significant variations in the rate of cholesterol synthesis were observed with respect to gestational age in adrenal and liver tissues. An increase in cholesterol synthesis as gestational age advanced was found. A plateau was reached between 14–18 weeks in the case of the adrenal and around 14–15 weeks in the case of the liver, and then the rates declined somewhat up to 21 weeks gestation. We conclude that high rates of cholesterol synthesis occur in adrenal, liver, and testicular tissues. Based on previous estimations of cholesterol synthesis, as determined by the measurement of the specific activity of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase in liver tissue, the size of the fetal liver, and its rapid growth, it is concluded that the rate of cholesterol synthesis in this tissue is adequate to meet the requirements of the fetal adrenal for low density lipoprotein-cholesterol, providing that the cholesterol formed de novo in the liver appears in the plasma in the form of low density lipoprotein-cholesterol.