Regulation of sterol synthesis and of 3-hydroxy-3-methylglutaryl coenzyme A reductase by lipoproteins in glial cells in primary culture.

Although plasma lipoproteins have been demonstrated to have a major role in regulating cholesterol biosynthesis in extraneural cells, no data concerning such regulation are available for developing brain, when cholesterol synthesis is especially active. Glial primary cultures derived from neonatal rat brain and by morphological and biochemical criteria essentially exclusively composed of astrocytes were utilized to examine such regulation. When the primary cultures, which had been maintained in 10% fetal calf serum, were placed in 10% lipoprotein-poor serum on day 7 of culture, an induction of sterol synthesis (1.6-2.2-fold) and of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase-specific activity (1.5-2-fold) resulted after 24 hr. Addition of low-density lipoprotein (LDL) to the 10% lipoprotein-poor serum prevented the induction of both sterol synthesis and HMG-CoA reductase. However, addition of high-density lipoprotein (HDL) to the 10% lipoprotein-poor serum caused a 1.5-2-fold further induction of sterol synthesis relative to that in cultures containing 10% lipoprotein-poor serum alone. In contrast to the glial primary cultures, cultures of C-6 glioma cells responded to replacement of 10% fetal calf serum with 10% lipoprotein-poor serum with much more marked increases of sterol synthesis and HMG-CoA reductase. Although, as with the primary cultures, addition of LDL to the C-6 glioma cell cultures prevented the increases in sterol synthesis and reductase activity, addition of HDL had no effect. Thus, these results indicate that in developing glial cells in primary culture, cholesterol synthesis and HMG-CoA reductase are capable of responsiveness to both LDL and HDL.(ABSTRACT TRUNCATED AT 250 WORDS)