Progesterone derivatives increase expression of Krox-20 and Sox-10 in rat Schwann cells.
Neuroactive steroids, like progesterone (P) and its 5alpha-reduced derivatives dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), are involved in the control of Schwann cell proliferation and in the myelinating program of these cells. Here, we demonstrate that in culture of rat Schwann cells, P and its derivatives also increase expression of Sox-10 and Krox-20 (i.e., two transcription factors with a key role in Schwann cell physiology and in their myelinating program). Data obtained by quantitative RT-PCR analysis show that treatment with P, DHP, or THP increases mRNA levels of Krox-20. This stimulatory effect anticipates that exerted by P and DHP on Sox-10 gene expression. Thus, although the effect on Krox-20 occurs after 1 h, that on Sox-10 reaches a peak after 2 h. A similar pattern of effect is also evident on their protein levels. As evaluated by Western blot analysis, Krox-20 is increased after 3 h of treatment with P, DHP, or THP, whereas P or DHP stimulates the expression of Sox-10 after 6 h of exposure. A computer analysis performed on rat and human promoters of these two transcription factors shows that putative P-responsive elements are present in Krox-20 but not in Sox-10. Interestingly, many putative binding sites for Krox-20 are present in the Sox-10 promoter. The observations reported here, together with the concept that P and its derivatives are able to influence directly the expression of myelin proteins, suggest that these neuroactive steroids might coordinate the Schwann cell-myelinating program utilizing different intracellular pathways.
Magnaghi
Valerio
V
Department of Endocrinology and Center of Excellence of Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy.
Ballabio
Marinella
M
Roglio
Ilaria
I
Melcangi
Roberto C
RC
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D011374:Progesterone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D055757:SOXE Transcription Factors; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D006609:High Mobility Group Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C527925:Sox10 protein, rat; D014157:Transcription Factors; D011374:Progesterone