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

Christine Patte-Mensah, Vincent Kappes, Marie José Freund-Mercier, Kazuyoshi Tsutsui, Ayikoe G. Mensah-Nyagan*

*この研究の対応する著者

研究成果: Article査読

79 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1233-1246
ページ数14
ジャーナルJournal of Neurochemistry
86
5
出版ステータスPublished - 2003 9月
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 細胞および分子神経科学

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