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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
Article

Abstract

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.

Keywords

Myelination P450scc Pregnenolone Schwann cell cAMP Steroid 

Abbreviations

3β-HSD

3β-Hydroxysteroid dehydrogenase/Δ5–Δ4 isomerase

AMG

Aminoglutethimide

cAMP

Cyclic adenosine monophosphate

db-cAMP

Dibutyryl cAMP

DHP

5α-Dihydroprogesterone

DMEM

Dulbecco’s Modified Eagle Medium

DMS

Defined medium for Schwann cells

GABA

Gamma-aminobutyric acid

L19

Ribosomal protein L19

MAG

Myelin associated glycoprotein

MBP

Myelin basic protein

P0

Myelin protein zero

P450scc

P450 side-chain cleavage

PMP-22

Peripheral myelin protein-22

Preg

Pregnenolone

RT-PCR

Reverse transcription-polymerase chain reaction

THP

5α,3α-Tetrahydroprogesterone

Notes

Acknowledgments

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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