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Progesterone and the oligodendroglial lineage: Stage‐dependent biosynthesis and metabolism
Author(s) -
Gago Nathalie,
Akwa Yvette,
Sananès Nicole,
Guennoun Rachida,
Baulieu Etienne Emile,
ElEtr Martine,
Schumacher Michael
Publication year - 2001
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.1117
Subject(s) - biology , oligodendrocyte , pregnenolone , neuroactive steroid , remyelination , biochemistry , progenitor cell , enzyme , cell type , metabolism , microbiology and biotechnology , receptor , cell , central nervous system , endocrinology , myelin , gabaa receptor , steroid , stem cell , hormone
Abstract Evidence has been accumulated showing that neurosteroids, particularly progesterone (PROG) and its metabolites, may participate in myelination and remyelination in the peripheral nervous system, but very few studies have been undertaken in the central nervous system (CNS). The aim of this work was to investigate the capacities of synthesis and metabolism of PROG at three important stages of the oligodendroglial lineage: oligodendrocyte pre‐progenitors (OPP), oligodendrocyte progenitors (OP), and fully differentiated oligodendrocytes (OL). Experiments have been conducted in vitro using highly purified primary cell cultures from rat brain. Cells were incubated with 3 H‐pregnenolone ( 3 H‐PREG), the immediate precursor of PROG, or with 3 H‐PROG, and steroids metabolites were then identified by thin layer chromatography and high‐performance liquid chromatography (HPLC). mRNA expression of key steroidogenic enzymes was evaluated by reverse transcription‐polymerase chain reaction (RT‐PCR). The results showed that only OPP and OP, but not OL, expressed 3β‐hydroxysteroid dehydrogenase/Δ5‐Δ4 isomerase mRNA and were able to synthesize PROG from PREG. In the three cell types studied, PROG was metabolized by the type 1 isoform of 5α‐reductase into 5α‐dihydroprogesterone (5α‐DHPROG). This enzyme exhibited a 5‐fold higher activity in OL than in OPP and OP. 5α‐DHPROG was further transformed either into 3α,5α‐tetrahydroprogesterone (3α,5α‐THPROG), known as a positive allosteric modulator of the GABA A receptor, or into the 3β‐isomer. The 3α,5α‐THPROG synthesis was 10 times higher in OPP than in the other cell studied, while the 3β,5α‐THPROG production did not change with cell differentiation. PROG synthesis and metabolism and the dramatic changes in neurosteroidogenesis observed during the oligodendroglial differentiation may contribute to oligodendrocyte development or the myelination process. GLIA 36:295–308, 2001. © 2001 Wiley‐Liss, Inc.