Cholesterol dynamics in the foetal and neonatal brain as reflected by circulatory levels of 24S-hydroxycholesterol.
Oxysterols, particularly those hydroxylated in the steroid side-chain, are formed from cholesterol by specific cytochrome P450 enzymes and may facilitate elimination of cholesterol from extrahepatic sources. In humans, the greatest portion of circulating 24S-hydroxycholesterol (24S-OH-Chol) is derived from the brain and the absolute concentration depends on age. In the present study, concentrations of 24S-OH-Chol and for comparison 27-OH-Chol were determined by a highly sensitive isotope dilution method using gas chromatography-mass spectrometry in serum samples from normal preterm and term neonates and those with Rhesus haemolytic disease, taken serially for diagnostic purposes. Serum concentrations of cholesterol, 24S-OH-Chol and 27-OH-Chol were similar in venous versus arterial cord blood of 6 term neonates. Serum concentrations of 24S-OH-Chol and 27-OH-Chol in 12 small for gestational age (SGA) preterm neonates were significantly lower than those in 12 appropriate for gestational age (AGA) preterm neonates (p < 0.001), and also lower than those in 12 SGA (0 < 0.001) and 12 AGA term neonates (p < 0.05). Serum cholesterol was significantly higher in preterm than in term neonates (p < 0.001). 24S-OH-Chol serially determined in 8 infants with Rhesus haemolytic disease increased 5-6-fold during the first 3 mo after birth (from 42 +/- 20 ng ml(-1) to 227 +/- 71 ng ml(-1)). 27-OH-Chol increased simultaneously from 30 +/- 14 ng ml(-1) to 100 +/- 39 ng ml(-1).


CONCLUSIONS
Serum concentrations of 24S-OH-Chol increased 5-6-fold after birth. This could be an indication of normal cholesterol metabolism in the developing neonatal brain.
Lütjohann
D
D
Department of Clinical Pharmacology, University of Bonn, Germany. d.luetjohann@uni-bonn.de
Björkhem
I
I
Locatelli
S
S
Dame
C
C
Schmolling
J
J
von Bergmann
K
K
Fahnenstich
H
H
D001921:Brain / Q000378:metabolism*; D002784:Cholesterol / Q000493:pharmacokinetics*; D004899:Erythroblastosis, Fetal / Q000097:blood; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D007231:Infant, Newborn / Q000378:metabolism*; D007234:Infant, Premature / Q000097:blood; D007236:Infant, Small for Gestational Age / Q000378:metabolism; D008137:Longitudinal Studies
D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol; D002784:Cholesterol