Molecular and Cellular Biochemistry

, Volume 313, Issue 1–2, pp 79–89 | Cite as

Regulatory role of cytochrome P450scc and pregnenolone in myelination by rat Schwann cells

  • Thant S. Zhu
  • Michael GlaserEmail author


To investigate the production of steroid hormones by Schwann cells and to examine the regulation of steroid hormone production during myelination, cultures of rat Schwann cells were differentiated into their myelinating phenotype in the absence of neurons with dibutyryl cAMP (db-cAMP). During this process, the expression of P450scc (involved in steroid biosynthesis) was elevated at both the mRNA and protein levels as evident in RT-PCR, Western blots, and immunostaining. Labeling of the cells with [14C] acetate revealed enhanced production of pregnenolone during differentiation into the myelinating phenotype. Disruption of P450scc’s activity with an inhibitor diminished the extent of differentiation into the myelinating phenotype as levels of mRNA and protein expression of myelin protein zero (P0) declined. However, the effect was reversed with the addition of pregnenolone. Furthermore, when the differentiating cultures were treated with pregnenolone, mRNA expression of P0 was upregulated, suggesting the stimulation of the differentiation process. Together, these results provide evidence for Schwann cells as a major producer of steroid hormones and pregnenolone production by P450scc as an important regulatory step during myelination.


Myelination P450scc Pregnenolone Schwann cell cAMP Steroid 



3β-Hydroxysteroid dehydrogenase/Δ5–Δ4 isomerase




Cyclic adenosine monophosphate


Dibutyryl cAMP




Dulbecco’s Modified Eagle Medium


Defined medium for Schwann cells


Gamma-aminobutyric acid


Ribosomal protein L19


Myelin associated glycoprotein


Myelin basic protein


Myelin protein zero


P450 side-chain cleavage


Peripheral myelin protein-22




Reverse transcription-polymerase chain reaction





The authors are grateful to Dr. H. Edward Conrad for helpful advice and suggestions. This work was funded in part by grants from the Multiple Sclerosis Society and the American Heart Association (Midwest Affiliate).


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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of IllinoisUrbanaUSA

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