Anatomical and cellular localization of neuroactive 5 alpha/3 alpha-reduced steroid-synthesizing enzymes in the spinal cord.
The complementary activities of 5 alpha-reductase (5 alpha-R) and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) are crucial for the synthesis of neuroactive 5 alpha/3 alpha-reduced steroids, such as 3 alpha-androstanediol, allopregnanolone, and tetrahydrodeoxycorticosterone, which control several important neurophysiological mechanisms through allosteric modulation of gamma-aminobutyric acid type A receptors. Immunocytochemical localization of 3 alpha-HSD in the central nervous system (CNS) has never been determined. The presence and activity of 5 alpha-R have been investigated in the CNS, but only the brain was considered; the spinal cord (SC) received little attention, although this structure is crucial for many sensorimotor activities. We have determined the first cellular distribution of 5 alpha-reductase type 1 (5 alpha-R1) and type 2 (5 alpha-R2) and 3 alpha-HSD immunoreactivities in adult rat SC. 5 alpha-R1 immunostaining was detected mainly in the white matter (Wm). In contrast, intense 5 alpha-R2 labeling was observed in dorsal (DH) and ventral horns of gray matter (Gm). 3 alpha-HSD immunoreactivity was largely distributed in the Wm and Gm, but the highest density was found in sensory areas of the DH. Double-labeling experiments combined with confocal analysis revealed that, in the Wm, 5 alpha-R1 was localized in glial cells, whereas 35% of 5 alpha-R2 and 3 alpha-HSD immunoreactivities were found in neurons. In the DH, 60% of 5 alpha-R2 immunostaining colocalized with oligodendrocyte, 25% with neuron, and 15% with astrocyte markers. Similarly, 45% of 3 alpha-HSD immunoreactivity was found in oligodendrocytes, 35% in neurons, and 20% in astrocytes. These results are the first demonstrating that oligodendrocytes and neurons of the SC possess the key enzymatic complex for synthesizing potent neuroactive steroids that may control spinal sensorimotor processes.
Laboratoire de Neurophysiologie Cellulaire et Intégrée, Unité Mixte de Recherche 7519-Centre National de la Recherche Scientifique, Université Louis Pasteur, 67084 Strasbourg, France.
Christine
C
Patte-Mensah
Trevor M
TM
Penning
Ayikoe G
AG
Mensah-Nyagan
D015096:3-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000378:metabolism*; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D000315:Adrenalectomy / Q000379:methods; D000818:Animals; D002452:Cell Count / Q000379:methods; D005110:Extracellular Space / Q000201:enzymology; D005260:Female; D005699:Galactosylceramides / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009457:Neuroglia / Q000145:classification / Q000201:enzymology; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000201:enzymology*; D011863:Radioimmunoassay; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology*
D005699:Galactosylceramides; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; C002454:galactocerebroside; D015096:3-Hydroxysteroid Dehydrogenases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase