ASTROCYTES SYNTHESIZE AND SECRETE THE LIPOPHILIC LIGAND CARRIER APOLIPOPROTEIN-D

EXPRESSION of the lipophilic ligand transporter, apolipoprotein D (apo D) by primary astrocyte cultures derived from neonatal mouse brain was investigated. Western blot analysis of cell lysates and media showed that apoD is constitutively secreted by astrocytes with little intrace llular storage. The secreted apoD floated primarily at density 1.063-1 .21 g ml(-1) upon sequential ultracentrifugation indicating its associ ation with lipids. Treatment of astrocytes with the carboxylic ionopho re, monensin, resulted in intracellular retention and decreased secret ion of apoD that was of slightly reduced M(r). Progesterone, a steroid hormone that binds to apoD with high affinity (10(-6) mol l(-1)) and the oxysterol, 25-hydroxycholesterol which is a potent regulator of ce llular cholesterol homeostasis in mammalian cells, differentially stim ulated apoD, but not apoE secretion. These results show that astrocyte s synthesize and constitutively secrete apoD and suggest a physiologic role for this lipocalin in cholesterol metabolism in the nervous syst em.