Biosynthesis and action of neurosteroids

被引:231
作者
Mellon, SH [1 ]
Griffin, LD [1 ]
Compagnone, NA [1 ]
机构
[1] Univ Calif San Francisco, Ctr Reprod Sci, Metab Res Unit, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
关键词
P450scc; P450c17; neurosteroid; cholinergic neuron; neurodegenerative disease; NP-C; transcription; gene expression;
D O I
10.1016/S0165-0173(01)00109-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Over the past decade, it has become clear that the brain, like the gonad, adrenal and placenta, is a steroidogenic organ. However, unlike classic steroidogenic tissues, the synthesis of steroids in the nervous system requires the coordinate expression and regulation of the genes encoding the steroidogenic enzymes in several different cell types (neurons and glia) at different locations in the nervous system, and at distances from the cell bodies. The steroids synthesized by the brain and nervous system, given the name neurosteroids, have a wide variety of diverse functions. In general, they mediate their actions, not through classic steroid hormone nuclear receptors, but through other mechanisms such as through ion gated neurotransmitter receptors, or through direct or indirect modulation of other neurotransmitter receptors. We have briefly summarized the biochemistry of the enzymes involved in the biosynthesis of neurosteroids, their localization during development and in the adult, and the regulation of their expression, highlighting both similarities and differences between expression in the brain and in classic steroidogenic tissues. (C) 2001 Elsevier Science BY. All rights reserved.
引用
收藏
页码:3 / 12
页数:10
相关论文
共 72 条
[1]   ANTICONVULSANT STEROIDS AND THE GABA BENZODIAZEPINE RECEPTOR-CHLORIDE IONOPHORE COMPLEX [J].
BELELLI, D ;
LAN, NC ;
GEE, KW .
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 1990, 14 (03) :315-322
[2]   5-ALPHA-PREGNAN-3-ALPHA,20-ALPHA-DIOL BEHAVES LIKE A PARTIAL AGONIST IN THE MODULATION OF GABA-STIMULATED CHLORIDE-ION UPTAKE BY SYNAPTONEUROSOMES [J].
BELELLI, D ;
GEE, KW .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 167 (01) :173-176
[3]  
BRINTON RD, 1994, J NEUROSCI, V14, P2763
[4]   Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis [J].
Carstea, ED ;
Morris, JA ;
Coleman, KG ;
Loftus, SK ;
Zhang, D ;
Cummings, C ;
Gu, J ;
Rosenfeld, MA ;
Pavan, WJ ;
Krizman, DB ;
Nagle, J ;
Polymeropoulos, MH ;
Sturley, SL ;
Ioannou, YA ;
Higgins, ME ;
Comly, M ;
Cooney, A ;
Brown, A ;
Kaneski, CR ;
BlanchetteMackie, EJ ;
Dwyer, NK ;
Neufeld, EB ;
Chang, TY ;
Liscum, L ;
Strauss, JF ;
Ohno, K ;
Zeigler, M ;
Carmi, R ;
Sokol, J ;
Markie, D ;
ONeill, RR ;
vanDiggelen, OP ;
Elleder, M ;
Patterson, MC ;
Brady, RO ;
Vanier, MT ;
Pentchev, PG ;
Tagle, DA .
SCIENCE, 1997, 277 (5323) :228-231
[5]  
CELOTTI F, 1992, FRONT NEUROENDOCRIN, V13, P163
[6]   DIFFERENTIAL DISTRIBUTION OF THE 5-ALPHA-REDUCTASE IN THE CENTRAL-NERVOUS-SYSTEM OF THE RAT AND THE MOUSE - ARE THE WHITE MATTER STRUCTURES OF THE BRAIN TARGET TISSUE FOR TESTOSTERONE ACTION [J].
CELOTTI, F ;
MELCANGI, RC ;
NEGRICESI, P ;
BALLABIO, M ;
MARTINI, L .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1987, 26 (01) :125-129
[7]   Novel role for the nuclear phosphoprotein SET in transcriptional activation of P450c17 and initiation of neurosteroidogenesis [J].
Compagnone, NA ;
Zhang, P ;
Vigne, JL ;
Mellon, SH .
MOLECULAR ENDOCRINOLOGY, 2000, 14 (06) :875-888
[8]   Neurosteroids: Biosynthesis and function of these novel neuromodulators [J].
Compagnone, NA ;
Mellon, SH .
FRONTIERS IN NEUROENDOCRINOLOGY, 2000, 21 (01) :1-56
[9]   STEROIDOGENIC ENZYME P450C17 IS EXPRESSED IN THE EMBRYONIC CENTRAL-NERVOUS-SYSTEM [J].
COMPAGNONE, NA ;
BULFONE, A ;
RUBENSTEIN, JLR ;
MELLON, SH .
ENDOCRINOLOGY, 1995, 136 (11) :5212-5223
[10]   Expression of steroid sulfatase during embryogenesis [J].
Compagnone, NA ;
Salido, E ;
Shapiro, LJ ;
Mellon, SH .
ENDOCRINOLOGY, 1997, 138 (11) :4768-4773