Pregnenolone metabolism in rodent embryonic neurons and astrocytes

The rat CNS has been previously shown to synthesize pregnenolone (PREG) and to convert it into progesterone (PROG) and some of its 5 alpha-reduced metabolites. However, the brain cell types involved in the metabolic conversions of PREG are poorly known. Selective conditions were used to obtain purified cultures of neurons and astrocytes from mouse or rat fetal striatum and cerebral cortex. Neurons converted PREG to only one identified metabolite, 20 alpha-dihydro PREG, whereas astrocytes converted PREG also to PROG, 5 alpha-dihydro PROG, and 3 alpha (3 beta)-5 alpha-tetrahydro PROG. Therefore, astrocytes can convert the neurosteroid PREG into the steroid hormone PROG and the neuromodulatory steroid 3 alpha, 5 alpha-tetrahydro PROG, whereas neurons lack the delta 5-3 beta-hydroxysteroid dehydrogenase isomerase activity (and cholesterol side-chain cleavage activity), necessary for the biosynthesis of PROG. Provision of steroid substrates is another example of cross-talk between glial cells and neurons.