To investigate the role of steroid receptors in mediating the reported effects of steroids on Schwann cell (SC) myelination and growth, we determined mRNA contents and transcriptional activities of the corticosteroid (glucocorticosteroid, GR, and mineralocorticosteroid, MR) receptors and sex steroid (progesterone, androgen and estrogen and ) receptors in rat SC cultured under proliferative (in the presence of insulin and forskolin which induces a high intracellular cAMP content) and quiescent conditions. We found no or very low expression and activity of the sex steroid receptors, as shown by mRNA concentrations determined with real-time PCR and transcriptional activities using transient expression of reporter plasmids in SC. These data and binding studies in SC lines demonstrated that the levels of the sex steroid receptors were the limiting factors. GR was clearly expressed (8000 sequences/ng total RNA) and functional. No significant modification in GR mRNA levels was observed but an increase in transcriptional efficiency was recorded in proliferating cells compared with quiescent cells. MR was also significantly expressed at the mRNA level (450 sequences/ng total RNA) under the two culture conditions. No MR transcriptional activity was observed in SC but a low specific binding of aldosterone was detected in SC lines. 11-hydroxysteroid-dehydrogenase type 2 (HSD2), an enzyme which inactivates glucocorticoids, was strongly expressed and active in quiescent SC while in proliferating cells HSD2 exhibited a strong decrease in activity and mRNA concentration. These data support a physiological role for HSD2 regulation of glucocorticosteroid concentrations in nerve SC.