Cellular distribution and bioactivity of the key steroidogenic enzyme, cytochrome P450side chain cleavage, in sensory neural pathways

• Published in: Journal of neurochemistry 2003-09, Vol.86 (5), p.1233-1246
• Main Authors: Patte‐Mensah, Christine, Kappes, Vincent, Freund‐Mercier, Marie‐José, Tsutsui, Kazuyoshi, Mensah‐Nyagan, Ayikoe G.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain Stem - cytology; Brain Stem - enzymology; Cholesterol - metabolism; Cholesterol Side-Chain Cleavage Enzyme - analysis; Cholesterol Side-Chain Cleavage Enzyme - antagonists & inhibitors; Cholesterol Side-Chain Cleavage Enzyme - metabolism; cytochrome P450side chain cleavage; Enzyme Inhibitors - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Ganglia, Spinal - enzymology; Immunohistochemistry; Male; Neural Pathways - cytology; Neural Pathways - enzymology; Neurons, Afferent - cytology; Neurons, Afferent - enzymology; neurosteroids; nociception; Organ Specificity; pain; Pregnenolone - analysis; Pregnenolone - biosynthesis; Rats; Rats, Sprague-Dawley; sensory system; Somatosensory Cortex - cytology; Somatosensory Cortex - enzymology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Spinal Cord - cytology; Spinal Cord - enzymology; steroids and nervous system; Thalamus - cytology; Thalamus - enzymology; Tritium; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2003.01935.x

Neurosteroids are steroids produced within the nervous system. Based on behavioural responses evoked in animals by synthetic steroid injections, several studies suggested neurosteroid involvement in important neurophysiological processes. These observations should be correlated only to neuroactive effects of the injected steroids. Neurosteroids mostly control the CNS activity through allosteric modulation of neurotransmitter receptors within concentration ranges used by neurotransmitters themselves. Therefore, neurosteroid production within pathways controlling a neurophysiological process is necessary to consider neurosteroid involvement in that process. Because of the increasing speculation about pain modulation by neurosteroids based on pharmacological observations, we decided to clarify the situation by investigating neurosteroidogenesis occurrence in sensory pathways, particularly in nociceptive structures. We studied the presence and activity of cytochrome P450side chain cleavage (P450scc) in rat pain pathways. P450scc‐immunoreactive cells were localized in dorsal root ganglia (DRG), spinal cord (SC) dorsal horn, nociceptive supraspinal nuclei (SSN) and somatosensory cortex. Incubation of DRG, SSN or SC tissue homogenates with [3H]cholesterol yielded the formation of radioactive metabolites including [3H]pregnenolone of which the synthesis was reduced in presence of aminogluthetimide, a P450scc inhibitor. These first neuroanatomical and neurochemical results demonstrate the occurrence of neurosteroidogenesis in nociceptive pathways and strongly suggest that neurosteroids may control pain mechanisms.