PMID- 10433246
OWN - NLM
STAT- MEDLINE
DCOM- 19990817
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 140
IP  - 8
DP  - 1999 Aug
TI  - Neurosteroidogenesis in astrocytes, oligodendrocytes, and neurons of cerebral 
      cortex of rat brain.
PG  - 3843-52
AB  - The brain is a steroidogenic organ that expresses steroidogenic enzymes and 
      produces neurosteroids. Although considerable information is now available 
      regarding the steroidogenic capacity of the brain, little is known regarding the 
      steroidogenic pathway and relative contributions of astrocytes, oligodendrocytes, 
      and neurons to neurosteroidogenesis. In the present study, we investigated 
      differential gene expression of the key steroidogenic enzymes using RT-PCR and 
      quantitatively evaluated the production of neurosteroids by highly purified 
      astrocytes, oligodendrocytes, and neurons from the cerebral cortex of neonatal 
      rat brains using specific and sensitive RIAs. Astrocytes appear to be the most 
      active steroidogenic cells in the brain. These cells express cytochrome P450 
      side-chain cleavage (P450scc), 17alpha-hydroxylase/C17-20-lyase (P450c17), 
      3beta-hydroxysteroid dehydrogenase (3betaHSD), 17beta-hydroxysteroid 
      dehydrogenase (17betaHSD), and cytochrome P450 aromatase (P450arom) and produce 
      pregnenolone (P5), progesterone (P4), dehydroepiandrosterone (DHEA), 
      androstenedione (A4), testosterone (T), estradiol, and estrone. Oligodendrocytes 
      express only P450scc and 3betaHSD and produce P5, P4, and A4. These cells do not 
      express P450c17, 17betaHSD, or P450arom or produce DHEA, T, or estrogen. Neurons 
      express P450scc, P450c17, 3betaHSD, and P450arom and produce P5, DHEA, A4, and 
      estrogen, but do not express 17betaHSD or produce T. By comparing the ability of 
      each cell type in the production of neurosteroids, astrocytes are the major 
      producer of P4, DHEA, and androgens, whereas oligodendrocytes are predominantly 
      the producer of P5 and neurons of estrogens. These findings serve to define the 
      neurosteroidogenic pathway, with special emphasis on the dominant role of 
      astrocytes and their interaction with oligodendrocytes and neurons in the genesis 
      of DHEA and active sex steroids. Thus, we propose that neurosteroidogenesis is 
      accomplished by a tripartite contribution of the three cell types in the brain.
FAU - Zwain, I H
AU  - Zwain IH
AD  - Department of Reproductive Medicine, University of California-San Diego School of 
      Medicine, La Jolla 92093-0633, USA. izwain@ucsd.edu
FAU - Yen, S S
AU  - Yen SS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Androgens)
RN  - 0 (Estrogens)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 73R90F7MQ8 (Pregnenolone)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - Androgens/*biosynthesis
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/cytology/*metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/*metabolism
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Estrogens/*biosynthesis
MH  - Hydroxysteroid Dehydrogenases/metabolism
MH  - Immunohistochemistry
MH  - Models, Chemical
MH  - Neurons/cytology/*metabolism
MH  - Oligodendroglia/cytology/*metabolism
MH  - Pregnenolone/*biosynthesis
MH  - Progesterone/*biosynthesis
MH  - Radioimmunoassay
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 1999/08/05 00:00
MHDA- 1999/08/05 00:01
CRDT- 1999/08/05 00:00
PHST- 1999/08/05 00:00 [pubmed]
PHST- 1999/08/05 00:01 [medline]
PHST- 1999/08/05 00:00 [entrez]
AID - 10.1210/endo.140.8.6907 [doi]
PST - ppublish
SO  - Endocrinology. 1999 Aug;140(8):3843-52. doi: 10.1210/endo.140.8.6907.