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.
Patte-Mensah
Christine
C
Laboratoire de Neurophysiologie Cellulaire et Intégrée, Unité Mixte de Recherche 7519-Centre National de la Recherche Scientifique, Université Louis Pasteur, 67084 Strasbourg, France.
Penning
Trevor M
TM
Mensah-Nyagan
Ayikoe G
AG
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