Sources of cholesterol for kidney and nerve during development

Rats were injected intraperitoneally with [3H]water; 2 h later, they were killed, dissected, and cholesterol was isolated from several tissues. Measurement of incorporated radioactivity allowed for calculation of the absolute amount of newly synthesized cholesterol appearing in a tissue. We determined the daily rate of synthesis of cholesterol in the sciatic nerve and kidney of rats at 10 time points between birth and 35 days of age. We compared this to the daily rate of accumulation of total cholesterol. For the sciatic nerve, total accumulation of cholesterol during development was always matched by accumulation of newly synthesized cholesterol, indicating that sciatic nerve synthesizes all of its own cholesterol. This was so independently of whether, at weaning, animals were placed on a cholesterol-free diet or a 2% cholesterol-containing diet. In contrast, in kidney, during the suckling period, only 25% of the accumulated cholesterol was newly synthesized; the remainder came from the circulation. Upon weaning to a 2% cholesterol-containing diet, there was increased local synthesis of cholesterol in kidney, so that within a few days about 50% was locally synthesized. If, however, the animals were weaned onto a cholesterol-free diet, there appeared to be further up-regulation of cholesterol biosynthesis in kidney; now all of the cholesterol accumulating was accounted for by that newly synthesized. Thus, the nerve is invariant with respect to self sufficiency for cholesterol; the kidney changes in this regard during development and as a function of diet.