Plasma levels of 24S-hydroxycholesterol reflect the balance between cerebral production and hepatic metabolism and are inversely related to body surface

We have previously presented evidence that most of the 24S-hydroxycholester ol present in the circulation originates from the brain and that most of th e elimination of this oxysterol occurs in the liver. Plasma 24S-hydroxychol esterol levels decline by a factor of about 5 during the first decades of l ife. The concentration of the enzyme cholesterol 24S-hydroxylase in the bra in is, however, about constant from the first year of life, and reduced enz yme levels thus cannot explain the decreasing plasma levels during infancy. In the present work we tested the hypothesis that the plasma levels of 24S -hydroxycholesterol may reflect the size of the brain relative to the capac ity of the liver to eliminate the substance. It is shown here that the age- dependent changes in absolute as well as cholesterol-related plasma level o f 24S-hydroxycholesterol closely follow the changes in the ratio between es timated brain weight and estimated liver volume. The size of the brain is i ncreased only about 50% whereas the size of the liver is increased by about g-fold after the age of 1 year. Liver volume is known to be highly correla ted to body surface, and in accordance with this the absolute as well as th e cholesterol-related plasma level of 24S-hydroxycholesterol was found to b e highly inversely correlated to body surface in 77 healthy subjects of var ying ages (r(2) = 0.74), Two chondrodystrophic dwarves with normal size of the brain but with markedly reduced body area had increased levels of 24S-h ydrorxycholesterol when related to age but normal levels when related to bo dy surface. It is concluded that the balance between cerebral production an d hepatic metabolism is a critical determinant for plasma levels of 24S-hyd roxycholesterol at different ages and that endocrinological factors are les s important. The results are discussed in relation to the possibility to us e 24S-hydrorn/cholesterol in the circulation as a marker for cholesterol ho meostasis in the brain. Plasma levels of 24S-hydroxycholesterol reflect the balance between cerebral production and hepatic metabolism and are inverse ly related to body surface.