Anatomical and cellular localization of neuroactive 5α/3α‐reduced steroid‐synthesizing enzymes in the spinal cord

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Abstract
The complementary activities of 5α‐reductase (5α‐R) and 3α‐hydroxysteroid dehydrogenase (3α‐HSD) are crucial for the synthesis of neuroactive 5α/3α‐reduced steroids, such as 3α‐androstanediol, allopregnanolone, and tetrahydrodeoxycorticosterone, which control several important neurophysiological mechanisms through allosteric modulation of γ‐aminobutyric acid type A receptors. Immunocytochemical localization of 3α‐HSD in the central nervous system (CNS) has never been determined. The presence and activity of 5α‐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 5α‐reductase type 1 (5α‐R1) and type 2 (5α‐R2) and 3α‐HSD immunoreactivities in adult rat SC. 5α‐R1 immunostaining was detected mainly in the white matter (Wm). In contrast, intense 5α‐R2 labeling was observed in dorsal (DH) and ventral horns of gray matter (Gm). 3α‐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, 5α‐R1 was localized in glial cells, whereas 35% of 5α‐R2 and 3α‐HSD immunoreactivities were found in neurons. In the DH, 60% of 5α‐R2 immunostaining colocalized with oligodendrocyte, 25% with neuron, and 15% with astrocyte markers. Similarly, 45% of 3α‐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. J. Comp. Neurol. 477:286–299, 2004.