Abstract
We have demonstrated the neuronal localization of neurosteroidogenic systems as well as the regulation of neurosteroidogenic activity in an adult rat hippocampus. The expressions of steroidogenic enzymes (cytochrome P450scc, adrenodoxin (ADX), NADPH-adrenodoxin reductase (ADR), hydroxysteroid sulfotransferase and steroidogenic acute regulatory protein (StAR)) were observed principally in pyramidal neurons and granule neurons by means of immunohistochemical staining. The expression of P450scc, redox partners, sulfotransferase and StAR was also confirmed by Western blot analysis.Exposing the neurons to N-methyl-D-aspartate (NMDA) stimulated the process of active neurosteroidogenesis. Upon stimulation with NMDA, the significant net production of pregnenolone (PREG) and pregnenolone sulfate (PREGS) was observed in the hippocampus. This neurosteroid production was considerably suppressed by the addition of antagonists of NMDA receptors, by Ca2+ depletion or by the addition of an inhibitor of P450scc. Upon stimulation with NMDA, the processing of full-length StAR (37-kDa) to the truncated 30-kDa StAR was observed. Taken together, these observations imply that hippocampal neurons synthesize neurosteroids. This synthesis may be stimulated and regulated by glutamate-mediated synaptic communication. We also discuss the possibility that PREGS may act as a paracrine modulator of NMDA receptors.
| Original language | English |
|---|---|
| Pages (from-to) | 127-137 |
| Number of pages | 11 |
| Journal | International Congress Series |
| Volume | 1233 |
| Issue number | C |
| DOIs | |
| Publication status | Published - 2002 Nov 1 |
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Keywords
- Calcium
- Hippocampus
- Neurosteroid
- NMDA
- P450scc
- StAR
- Sulfotransferase
ASJC Scopus subject areas
- Medicine(all)
Cite this
Cytochrome P450-dependent neurosteroid synthesis in the rat brain hippocampal neurons. / Kimoto, Tetsuya; Tsurugizawa, Tomokazu; Ohta, Yoichiro; Makino, Jun'ya; Tamura, Hiroomi; Hojo, Yasushi; Enami, Taihei; Kawato, Suguru.
In: International Congress Series, Vol. 1233, No. C, 01.11.2002, p. 127-137.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytochrome P450-dependent neurosteroid synthesis in the rat brain hippocampal neurons
AU - Kimoto, Tetsuya
AU - Tsurugizawa, Tomokazu
AU - Ohta, Yoichiro
AU - Makino, Jun'ya
AU - Tamura, Hiroomi
AU - Hojo, Yasushi
AU - Enami, Taihei
AU - Kawato, Suguru
PY - 2002/11/1
Y1 - 2002/11/1
N2 - We have demonstrated the neuronal localization of neurosteroidogenic systems as well as the regulation of neurosteroidogenic activity in an adult rat hippocampus. The expressions of steroidogenic enzymes (cytochrome P450scc, adrenodoxin (ADX), NADPH-adrenodoxin reductase (ADR), hydroxysteroid sulfotransferase and steroidogenic acute regulatory protein (StAR)) were observed principally in pyramidal neurons and granule neurons by means of immunohistochemical staining. The expression of P450scc, redox partners, sulfotransferase and StAR was also confirmed by Western blot analysis.Exposing the neurons to N-methyl-D-aspartate (NMDA) stimulated the process of active neurosteroidogenesis. Upon stimulation with NMDA, the significant net production of pregnenolone (PREG) and pregnenolone sulfate (PREGS) was observed in the hippocampus. This neurosteroid production was considerably suppressed by the addition of antagonists of NMDA receptors, by Ca2+ depletion or by the addition of an inhibitor of P450scc. Upon stimulation with NMDA, the processing of full-length StAR (37-kDa) to the truncated 30-kDa StAR was observed. Taken together, these observations imply that hippocampal neurons synthesize neurosteroids. This synthesis may be stimulated and regulated by glutamate-mediated synaptic communication. We also discuss the possibility that PREGS may act as a paracrine modulator of NMDA receptors.
AB - We have demonstrated the neuronal localization of neurosteroidogenic systems as well as the regulation of neurosteroidogenic activity in an adult rat hippocampus. The expressions of steroidogenic enzymes (cytochrome P450scc, adrenodoxin (ADX), NADPH-adrenodoxin reductase (ADR), hydroxysteroid sulfotransferase and steroidogenic acute regulatory protein (StAR)) were observed principally in pyramidal neurons and granule neurons by means of immunohistochemical staining. The expression of P450scc, redox partners, sulfotransferase and StAR was also confirmed by Western blot analysis.Exposing the neurons to N-methyl-D-aspartate (NMDA) stimulated the process of active neurosteroidogenesis. Upon stimulation with NMDA, the significant net production of pregnenolone (PREG) and pregnenolone sulfate (PREGS) was observed in the hippocampus. This neurosteroid production was considerably suppressed by the addition of antagonists of NMDA receptors, by Ca2+ depletion or by the addition of an inhibitor of P450scc. Upon stimulation with NMDA, the processing of full-length StAR (37-kDa) to the truncated 30-kDa StAR was observed. Taken together, these observations imply that hippocampal neurons synthesize neurosteroids. This synthesis may be stimulated and regulated by glutamate-mediated synaptic communication. We also discuss the possibility that PREGS may act as a paracrine modulator of NMDA receptors.
KW - Calcium
KW - Hippocampus
KW - Neurosteroid
KW - NMDA
KW - P450scc
KW - StAR
KW - Sulfotransferase
UR - http://www.scopus.com/inward/record.url?scp=85014808850&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014808850&partnerID=8YFLogxK
U2 - 10.1016/S0531-5131(02)00146-2
DO - 10.1016/S0531-5131(02)00146-2
M3 - Article
VL - 1233
SP - 127
EP - 137
JO - International Congress Series
JF - International Congress Series
SN - 0531-5131
IS - C
ER -