Neurosteroid progesterone is up-regulated in the brain of jimpy and shiverer mice.
Concentrations of neurosteroids have been measured in the brains of postnatal myelin mutants jimpy (jp) and shiverer (shi) mice and of their normal controls. Progesterone (PROG) concentrations were increased more than threefold in the brains of mutant mice. Marked astroglial reaction occurs in the brains of jp mice and to a much smaller extent in shi ones. Whereas the mitochondrial benzodiazepine/diazepam binding inhibitor (DBI) receptor (MBR) was below the immunohistochemical detection limit in normal mice (except in the choroid plexus and ependyma cells), it was significantly expressed in many reactive astrocytes of jp and shi mice brains. DBI-like peptides, investigated either by immunohistochemistry or by radioimmunoassay, were expressed to similar extents in mutant and control mice. Reversed-phase HPLC indicated that DBI-like peptides were almost exclusively of the triakontatetraneuropeptide size. It was concluded that the increased expression of MBR (involved in the intramitochondrial delivery of cholesterol to P450scc) likely accounts for the large PROG content in mutant mice brain. The role of PROG in myelin repair is discussed.
Le Goascogne
C
C
INSERM U 488, Bicêtre, France.
Eychenne
B
B
Tonon
M C
MC
Lachapelle
F
F
Baumann
N
N
Robel
P
P
D043582:5-alpha-Dihydroprogesterone; D000302:Adrenal Cortex / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D003345:Corticosterone / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D003711:Demyelinating Diseases / Q000378:metabolism*; D026261:Diazepam Binding Inhibitor; D007150:Immunohistochemistry; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008816:Mice, Jimpy / Q000378:metabolism*; D008818:Mice, Neurologic Mutants / Q000378:metabolism*; D009479:Neuropeptides / Q000032:analysis / Q000378:metabolism; D009928:Organ Specificity; D010446:Peptide Fragments; D011277:Pregnanediones / Q000378:metabolism; D011280:Pregnanolone / Q000378:metabolism; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*; D011863:Radioimmunoassay; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015854:Up-Regulation
D026261:Diazepam Binding Inhibitor; D009479:Neuropeptides; D010446:Peptide Fragments; D011277:Pregnanediones; D018160:Receptors, Cytoplasmic and Nuclear; C067529:diazepam binding inhibitor (33-50); C078199:diazepam-binding inhibitor receptor; D003687:Dehydroepiandrosterone; D011374:Progesterone; D019314:Dehydroepiandrosterone Sulfate; D011284:Pregnenolone; D043582:5-alpha-Dihydroprogesterone; D011280:Pregnanolone; D003345:Corticosterone