Expression and functional state of the corticosteroid receptors and 11 beta-hydroxysteroid dehydrogenase type 2 in Schwann cells.
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 and mineralocorticosteroid) receptors (GR and MR) and sex steroid (progesterone, androgen, and estrogen alpha and beta) 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 (approximately 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 (approximately 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 beta-Hydroxysteroid-dehydrogenase type 2 (HSD2), an enzyme that inactivates glucocorticoids, was strongly expressed and active in quiescent SC, although 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.
Groyer
Ghislaine
G
Unité Mixte de Recherche 788, Institut National de la Santé et de la Recherche Médicale and University Paris-Sud 11, 94276 Le Kremlin-Bicêtre, France.
Eychenne
Bernard
B
Girard
Christelle
C
Rajkowski
Krzysztof
K
Schumacher
Michael
M
Cadepond
Françoise
F
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology; D014158:Transcription, Genetic; D014162:Transfection
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005938:Glucocorticoids; D012739:Gonadal Steroid Hormones; D007328:Insulin; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D005576:Colforsin; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2