| Changes in 5alpha-pregnane steroids and neurosteroidogenic enzyme expression in the perinatal sheep. | |
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MedLine Citation:
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PMID: 12646725 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pregnane steroids have sedative and neuroprotective effects on the brain as a result of interactions with the steroid-binding site of the GABAA receptor. To determine whether the fetal brain is able to synthesize pregnane steroids de novo from cholesterol, we measured the expression of cytochrome P450 side-chain cleavage (P450scc) and 5alpha-reductase type II (5alphaRII) enzymes in fetal sheep from 72 to 144 d gestation (term approximately 147 d) and in newborn lambs at 3 and 19-26 d of age. Both P450scc and 5alphaRII expression was detectable by 90 d gestation in the major regions of the brain and also in the adrenal glands. Expression increased with advancing gestation and was either maintained at fetal levels or increased further after birth. In contrast, the relatively high content (200-400 pmol/g) of allopregnanolone (5alpha-pregnan-3alpha-ol-20-one), a major sedative 5alpha-pregnane steroid, present throughout the brain from 90 d gestation to term, was reduced significantly (<50 pmol/g) immediately after birth. These results suggest that although the perinatal brain has the enzymes potentially to synthesize pregnane steroids de novo from cholesterol, either the placenta is a major source of these steroids to the brain or other factors associated with intrauterine life may be responsible for high levels of allopregnanolone production in the fetal brain until birth. |
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Authors:
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Phuong N Nguyen; Saraid S Billiards; David W Walker; Jonathan J Hirst |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-03-19 |
Journal Detail:
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Title: Pediatric research Volume: 53 ISSN: 0031-3998 ISO Abbreviation: Pediatr. Res. Publication Date: 2003 Jun |
Date Detail:
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Created Date: 2003-06-02 Completed Date: 2004-01-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: United States |
Other Details:
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Languages: eng Pagination: 956-64 Citation Subset: IM |
Affiliation:
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Fetal and Neonatal Research Group, Department of Physiology, Monash University, Clayton Victoria 3800, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain / enzymology Cholestenone 5 alpha-Reductase / metabolism* Cholesterol Side-Chain Cleavage Enzyme / metabolism* Enzyme-Linked Immunosorbent Assay Female Pregnancy Pregnanolone / metabolism* Sheep / embryology* |
| Chemical | |
Reg. No./Substance:
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128-20-1/Pregnanolone; 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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