Early activation of transcription factor expression in Schwann cells by progesterone

Abstract

Progesterone (PROG) promotes the myelination of sciatic nerves during regeneration after cryolesion. But, little is known about the molecular mechanisms by which the hormone exerts its effects. This could be initiated by the regulation of transcription factor expression in Schwann cells, which produce the myelin sheaths in the peripheral nervous system. We investigated by RT-PCR whether PROG activated expression of transcription factors: Egr-1 (Krox-24) Egr-2 (Krox-20), Egr-3, c-jun, jun B, jun D, c-Fos, Fos B, Fra-1, Fra-2, CREB, ATF 4, SCIP and Sox-10 in cultured Schwann cells. PROG triggered a quick (visible as soon as 15 min), strong (6 to 18-fold) and transient (1–2 h) stimulation of Egr-1, Egr-2, Egr-3 and Fos B genes expression. Expression of other genes remained unaffected by PROG treatment. The same expression pattern was obtained in the MSC 80 line (mouse Schwann cells), but not in the NIH-3T3 and CHO lines. Estradiol and testosterone induced different patterns of transcription factor gene activation in Schwann cells. Serum stimulated all genes activated by PROG in addition c-fos, fra-1 and fra-2. The PROG effects were blocked by Actinomycin D and by RU 486. This suggests that the activation of these genes occurs at the transcriptional level via the interaction of the hormone with its cognate receptor. Thus, PROG can regulate Schwann cell functions and differentiation by transiently activating specific transcription factors.