Neurosteroids in rat sciatic nerves and Schwann cells.

Pregnenolone (PREG) and corticosterone were measured in sciatic nerves and plasma of adult male rats by radioimmunoassays. Concentrations of PREG were higher in nerves than in plasma, whereas those of corticosterone were lower. In contrast to corticosterone, PREG was not reduced by castration and adrenalectomy, strongly suggesting a local synthesis of this steroid independent of glandular sources. In fact, Schwann cells in culture produced PREG from 25-hydroxy-cholesterol. They also converted PREG and dehydroepiandrosterone to the respective 7 alpha-hydroxylated metabolites and to 5-androstene-3 beta,17 beta-diol. The metabolism of steroids was increased when Schwann cells were grown in the presence of insulin and forskolin. These findings may have important implications for understanding the regeneration of peripheral nerves.