Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction.
Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, 17beta-estradiol and testosterone as well as their sulfate esters. These brain neurosteroids are synthesized by cytochrome P450s (P450scc, P45017alpha and P450arom) from endogenous cholesterol. Synthesis is acutely dependent on the Ca(2+) 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.
Shibuya
Keisuke
K
Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo at Komaba, Meguro, 153, Tokyo, Japan.
Takata
Norio
N
Hojo
Yasushi
Y
Furukawa
Aizo
A
Yasumatsu
Nobuaki
N
Kimoto
Tetsuya
T
Enami
Taihei
T
Suzuki
Kumiko
K
Tanabe
Nobuaki
N
Ishii
Hirotaka
H
Mukai
Hideo
H
Takahashi
Taiki
T
Hattori
Taka-aki
TA
Kawato
Suguru
S
D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000096:biosynthesis; D004958:Estradiol / Q000096:biosynthesis; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000096:biosynthesis*; D011284:Pregnenolone / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis
D001141:Aromatase; D002784:Cholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003577:Cytochrome P-450 Enzyme System; D003687:Dehydroepiandrosterone; D004958:Estradiol; D018377:Neurotransmitter Agents; D011284:Pregnenolone; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D013254:Steroid 17-alpha-Hydroxylase; D013739:Testosterone