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, 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.
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo at Komaba, Meguro, 153, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shibuya
authors.forename: Norio
authors.initials: N
authors.lastname: Takata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hojo
authors.forename: Aizo
authors.initials: A
authors.lastname: Furukawa
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yasumatsu
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimoto
authors.forename: Taihei
authors.initials: T
authors.lastname: Enami
authors.forename: Kumiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanabe
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ishii
authors.forename: Hideo
authors.initials: H
authors.lastname: Mukai
authors.forename: Taiki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Hattori
authors.forename: Suguru
authors.initials: S
authors.lastname: Kawato
mesh_terms: 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
chemical_list: 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