Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction

Keisuke Shibuya; Norio Takata; Yasushi Hojo; Aizo Furukawa; Nobuaki Yasumatsu; Tetsuya Kimoto; Taihei Enami; Kumiko Suzuki; Nobuaki Tanabe; Hirotaka Ishii; Hideo Mukai; Taiki Takahashi; Taka aki Hattori; Suguru Kawato

doi:10.1016/S0304-4165(02)00489-0

Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction

Keisuke Shibuya, Norio Takata, Yasushi Hojo, Aizo Furukawa, Nobuaki Yasumatsu, Tetsuya Kimoto, Taihei Enami, Kumiko Suzuki, Nobuaki Tanabe, Hirotaka Ishii, Hideo Mukai, Taiki Takahashi, Taka aki Hattori, Suguru Kawato

Research output: Contribution to journal › Article › peer-review

121 Citations (Scopus)

Abstract

Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, 17β-estradiol and testosterone as well as their sulfate esters. These brain neurosteroids are synthesized by cytochrome P450s (P450scc, P45017α and P450arom) from endogenous cholesterol. Synthesis is acutely dependent on the Ca²⁺ influx attendant upon neuron-neuron communication via N-methyl-D-aspartate (NMDA) receptors. Pregnenolone sulfate, estradiol and corticosterone rapidly modulate neuronal signal transduction and the induction of long-term potentiation via NMDA receptors and putative membrane steroid receptors. Brain neurosteroids are therefore promising neuromodulators that may either activate or inactivate neuron-neuron communication, thereby mediating learning and memory in the hippocampus.

Original language	English
Pages (from-to)	301-316
Number of pages	16
Journal	Biochimica et Biophysica Acta - General Subjects
Volume	1619
Issue number	3
DOIs	https://doi.org/10.1016/S0304-4165(02)00489-0
Publication status	Published - 2003 Feb 17
Externally published	Yes

Keywords

Brain
Hippocampus
LTP
Neurosteroid
P450
Signal transduction

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

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Shibuya, K., Takata, N., Hojo, Y., Furukawa, A., Yasumatsu, N., Kimoto, T., Enami, T., Suzuki, K., Tanabe, N., Ishii, H., Mukai, H., Takahashi, T., Hattori, T. A., & Kawato, S. (2003). Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction. Biochimica et Biophysica Acta - General Subjects, 1619(3), 301-316. https://doi.org/10.1016/S0304-4165(02)00489-0

Shibuya, K, Takata, N, Hojo, Y, Furukawa, A, Yasumatsu, N, Kimoto, T, Enami, T, Suzuki, K, Tanabe, N, Ishii, H, Mukai, H, Takahashi, T, Hattori, TA & Kawato, S 2003, 'Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction', Biochimica et Biophysica Acta - General Subjects, vol. 1619, no. 3, pp. 301-316. https://doi.org/10.1016/S0304-4165(02)00489-0

@article{c5734f4f682c4f3c8f8e27626df468cc,

title = "Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction",

abstract = "Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, 17β-estradiol and testosterone as well as their sulfate esters. These brain neurosteroids are synthesized by cytochrome P450s (P450scc, P45017α and P450arom) from endogenous cholesterol. Synthesis is acutely dependent on the Ca2+ influx attendant upon neuron-neuron communication via N-methyl-D-aspartate (NMDA) receptors. Pregnenolone sulfate, estradiol and corticosterone rapidly modulate neuronal signal transduction and the induction of long-term potentiation via NMDA receptors and putative membrane steroid receptors. Brain neurosteroids are therefore promising neuromodulators that may either activate or inactivate neuron-neuron communication, thereby mediating learning and memory in the hippocampus.",

keywords = "Brain, Hippocampus, LTP, Neurosteroid, P450, Signal transduction",

author = "Keisuke Shibuya and Norio Takata and Yasushi Hojo and Aizo Furukawa and Nobuaki Yasumatsu and Tetsuya Kimoto and Taihei Enami and Kumiko Suzuki and Nobuaki Tanabe and Hirotaka Ishii and Hideo Mukai and Taiki Takahashi and Hattori, {Taka aki} and Suguru Kawato",

note = "Funding Information: We are very grateful to Prof. Douglas M. Stocco, Profs. Shiro Kominami and Takeshi Yamazaki at Hiroshima University, each of which have made an essential contribution to brain neurosteroid metabolism analysis. Members of the CREST Project on “Endocrine Disruptors in Synthesis and Action of Brain Neurosteroids” are highly acknowledged. We thank Dr. John Rose for the critical reading of the manuscript. This work is also supported by grants from the Ministry of Education, Science and Culture in Japan.",

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doi = "10.1016/S0304-4165(02)00489-0",

language = "English",

volume = "1619",

pages = "301--316",

journal = "Biochimica et Biophysica Acta - General Subjects",

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T1 - Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction

AU - Shibuya, Keisuke

AU - Takata, Norio

AU - Hojo, Yasushi

AU - Furukawa, Aizo

AU - Yasumatsu, Nobuaki

AU - Kimoto, Tetsuya

AU - Enami, Taihei

AU - Suzuki, Kumiko

AU - Tanabe, Nobuaki

AU - Ishii, Hirotaka

AU - Mukai, Hideo

AU - Takahashi, Taiki

AU - Hattori, Taka aki

AU - Kawato, Suguru

N1 - Funding Information: We are very grateful to Prof. Douglas M. Stocco, Profs. Shiro Kominami and Takeshi Yamazaki at Hiroshima University, each of which have made an essential contribution to brain neurosteroid metabolism analysis. Members of the CREST Project on “Endocrine Disruptors in Synthesis and Action of Brain Neurosteroids” are highly acknowledged. We thank Dr. John Rose for the critical reading of the manuscript. This work is also supported by grants from the Ministry of Education, Science and Culture in Japan.

PY - 2003/2/17

Y1 - 2003/2/17

N2 - Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, 17β-estradiol and testosterone as well as their sulfate esters. These brain neurosteroids are synthesized by cytochrome P450s (P450scc, P45017α and P450arom) from endogenous cholesterol. Synthesis is acutely dependent on the Ca2+ influx attendant upon neuron-neuron communication via N-methyl-D-aspartate (NMDA) receptors. Pregnenolone sulfate, estradiol and corticosterone rapidly modulate neuronal signal transduction and the induction of long-term potentiation via NMDA receptors and putative membrane steroid receptors. Brain neurosteroids are therefore promising neuromodulators that may either activate or inactivate neuron-neuron communication, thereby mediating learning and memory in the hippocampus.

AB - Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, 17β-estradiol and testosterone as well as their sulfate esters. These brain neurosteroids are synthesized by cytochrome P450s (P450scc, P45017α and P450arom) from endogenous cholesterol. Synthesis is acutely dependent on the Ca2+ influx attendant upon neuron-neuron communication via N-methyl-D-aspartate (NMDA) receptors. Pregnenolone sulfate, estradiol and corticosterone rapidly modulate neuronal signal transduction and the induction of long-term potentiation via NMDA receptors and putative membrane steroid receptors. Brain neurosteroids are therefore promising neuromodulators that may either activate or inactivate neuron-neuron communication, thereby mediating learning and memory in the hippocampus.

KW - Brain

KW - Hippocampus

KW - LTP

KW - Neurosteroid

KW - P450

KW - Signal transduction

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ER -

Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction

Abstract

Keywords

ASJC Scopus subject areas

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