title: Role of cytochrome p450 in synaptocrinology: endogenous estrogen synthesis in the brain hippocampus.
abstract: In the hippocampus, the center for learning and memory, cytochrome P450s (P450scc, P450(17alpha), and P450arom) as well as 17beta-, 3beta-hydroxysteroid dehydrogenases, and 5alpha-reductase participate in the synthesis of brain steroids from endogenous cholesterol. These brain steroids include pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone, and 17beta-estradiol. Both estrogens and androgens are synthesized in the adult male hippocampal neurons. Although the expression levels of steroidogenic enzymes are as low as 1/200 to 1/50,000 of those in testis or ovary, the levels of synthesized steroids are sufficient for the local usage within small neurons (i.e., intracrine system). This intracrine system contrasts with the endocrine system in which high expression levels of steroidogenic enzymes are necessary in endocrine organs in order to supply steroids to many other organs via blood circulation. Endogenous synthesis of sex steroids in the hypothalamus is also discussed. Rapid modulation by estrogens and xenoestrogens is discussed concerning synaptic plasticity such as the long-term potentiation, the long-term depression, or spinogenesis. Synaptic expression of P450(17alpha), P450arom, and estrogen receptors suggests "synaptocrine" mechanisms of brain steroids, which are synthesized at synapses and act as synaptic modulators.
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo at Komaba, Meguro, Tokyo, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Murakami
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanabe
authors.forename: Hiro-taka
authors.initials: HT
authors.lastname: Ishii
authors.forename: Mari
authors.initials: M
authors.lastname: Ogiue-Ikeda
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Tsurugizawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Mukai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hojo
authors.forename: Norio
authors.initials: N
authors.lastname: Takata
authors.forename: Aizo
authors.initials: A
authors.lastname: Furukawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimoto
authors.forename: Suguru
authors.initials: S
authors.lastname: Kawato
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism* / Q000502:physiology; D004967:Estrogens / Q000096:biosynthesis*; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D016253:Microscopy, Immunoelectron; D008959:Models, Neurological; D013569:Synapses / Q000502:physiology*
chemical_list: D004967:Estrogens; D003577:Cytochrome P-450 Enzyme System