Document Detail


Localization of p450scc and 5alpha-reductase type-2 in the cerebellum of fetal and newborn sheep.
MedLine Citation:
PMID:  11020552     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prenatally, neuroactive steroids that modulate GABAergic activity may be synthesized de novo within the fetal brain. We have examined changes in immunoreactivity staining for the steroidogenic enzymes cholesterol P450 side-chain cleavage (P450scc), and 5alpha-reductase type-2 in the cerebellum of late gestation (130-145 days gestation) fetal sheep and newborn lambs (1-4 weeks of age). Both enzymes were predominantly localized in the Purkinje cell body and dendrites of the fetal and newborn cerebellum, with weaker immunoreactivity in a few cells of the inner granular layer. P450scc immunoreactivity was present in Purkinje neurons expressing either of the neuronal microtubule associated proteins MAP1b/5 or MAP2a/b, but was absent from GFAP and HNK-1 positive cells. Soma of Purkinje neurons were also immunopositive for 5alpha-reductase type-2 in the fetuses, but expression decreased to just detectable levels in the 1-2 and 2-4 week old lambs. Both MAP1b/5- and MAP2a/b-positive Purkinje neurons showed 5alpha-reductase type-2 expression in the fetus, whereas the residual 5alpha-reductase staining in the newborn lamb was present only in MAP2a/b-positive Purkinje neurons. Allopregnanolone in the cerebellum decreased from 21.8+/-1.9 ng/g wet weight in fetuses at 140-145 days gestation to 6.7+/-0.5 ng/g in 2-4 week old lambs (P<0. 05). Thus, synthesis of neuroactive steroids from cholesterol is possible in cerebellar neurons in late gestation and persists into neonatal life, 5alpha-reductase type-2 expression is greater in the fetus compared to the neonate, and allopregnanolone concentrations in the cerebellum decrease significantly after birth.
Authors:
S Petratos; J J Hirst; S Mendis; P Anikijenko; D W Walker
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research. Developmental brain research     Volume:  123     ISSN:  0165-3806     ISO Abbreviation:  Brain Res. Dev. Brain Res.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2001-01-09     Completed Date:  2001-01-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8908639     Medline TA:  Brain Res Dev Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  81-6     Citation Subset:  IM    
Affiliation:
Department of Physiology, Monash University, Victoria 3800, Clayton, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn / metabolism*
Cerebellum / cytology,  embryology*,  enzymology*
Cholestenone 5 alpha-Reductase
Cholesterol Side-Chain Cleavage Enzyme / metabolism*
Female
Fluorescent Antibody Technique, Indirect
Oxidoreductases / metabolism*
Pregnancy
Pregnanolone / pharmacology
Purkinje Cells / drug effects,  enzymology,  metabolism
Receptors, GABA-A / metabolism
Sheep
Chemical
Reg. No./Substance:
0/Receptors, GABA-A; 128-20-1/Pregnanolone; EC 1.-/Oxidoreductases; EC 1.14.15.6/Cholesterol Side-Chain Cleavage Enzyme; EC 1.3.1.22/Cholestenone 5 alpha-Reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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