Mineralocorticoid and glucocorticoid receptors in sciatic nerve function and regeneration.
The contribution of the two corticosteroid (mineralocorticoid and glucocorticoid) receptor (MR and GR) pathways to the function and regeneration of the sciatic nerve was investigated. We found that the corticosterone-inactivating enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2) was up-regulated 7 days after lesion in freeze-injured nerve. The maintenance of a low intracellular level of corticosterone by HSD2 activity in the regenerating nerve is concordant with the improvement of nervous function in injured animals (as measured by walking ability) after treatment by the GR antagonist mifepristone and with the reduction in GR participation in accumulation of the mRNA for numerous endogenous genes (from the renin-angiotensin system and other classical mineralocorticoid-responsive genes), in the same animals. Furthermore, using the MR antagonist spironolactone, we demonstrated that MR plays an active role in the function of the intact sciatic nerve: MR is required for walking ability and participates in the control of the accumulation of the mRNA for several endogenous genes. However, after injury, changes in gene expression cannot be fully explained by changes in MR/GR activity, due to an HSD2 effect, and other signalling pathway(s) induced by the lesion likely combine with the effect of the corticosteroid receptors.
Girard
Christelle
C
Unité Mixte de Recherche 788, Inserm and Université Paris-Sud 11, 94276 Le Kremlin-Bicêtre, France.
Eychenne
Bernard
B
Schweizer-Groyer
Ghislaine
G
Cadepond
Françoise
F
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression; D000451:Mineralocorticoid Receptor Antagonists; D009416:Nerve Regeneration; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012084:Renin-Angiotensin System; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism / Q000502:physiology*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D016138:Walking
D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D015222:Sodium Channels; D000242:Cyclic AMP; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000254:Sodium-Potassium-Exchanging ATPase; D003345:Corticosterone