| Steroid production and excretion by the pregnant mouse, particularly in relation to pregnancies with fetuses deficient in Delta7-sterol reductase (Dhcr7), the enzyme associated with Smith-Lemli-Opitz syndrome. | |
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MedLine Citation:
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PMID: 19406241 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study has shown that the mouse has a great increase in steroid production during pregnancy in similar fashion to the human. Many steroids were provisionally identified in maternal urine of the wild-type mouse. The major progesterone metabolites appear to be hydroxylated pregnanolones, particularly with hydroxyl groups in the 16alpha position. Rather than estriol being the major end-product of feto-placental steroid synthesis as in the human, the pregnant mouse produces and excretes large amounts of androgen metabolites, ranging in polarity from androstanetriols to androstanepentols. These steroids have 15alpha- or 18-hydroxyl groups with additional hydroxylation at uncharacterized positions. From metabolite data the peak of pregnancy progesterone production appears to be between 7.5 and 14.5 gestational days, while for C(19) metabolites peak excretion is later. The starting-point of the studies was to study pregnancy steroid production by a mouse model for Smith-Lemli-Opitz syndrome, 7-dehydrosterol reductase (DHCR7) deficiency. In human pregnancies with DHCR7 deficient fetuses large amounts of 7- and 8-dehydrosteroids are excreted, products secondary to high fetal 7- and 8-dehydrocholesterol (DHC) accumulation. This agrees with existing evidence that human feto-placental steroid synthesis utilizes little maternal cholesterol as precursor. In contrast, this study has shown that pregnant mice carrying dhcr7 deficient fetuses with relatively high DHC production had essentially undetectable maternal excretions of steroids with Delta(7)- and Delta(8)-unsaturation. As mutant mouse mothers have essentially normal cholesterol production (little or no DHC build-up), this suggests maternal cholesterol is primarily utilized for pregnancy steroid synthesis in the mouse. |
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Authors:
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Xavier Matabosch; Mahbuba Rahman; Beverly Hughes; Shailendra B Patel; Gordon Watson; Cedric Shackleton |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-05-03 |
Journal Detail:
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Title: The Journal of steroid biochemistry and molecular biology Volume: 116 ISSN: 1879-1220 ISO Abbreviation: J. Steroid Biochem. Mol. Biol. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-06-26 Completed Date: 2009-10-26 Revised Date: 2010-09-01 |
Medline Journal Info:
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Nlm Unique ID: 9015483 Medline TA: J Steroid Biochem Mol Biol Country: England |
Other Details:
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Languages: eng Pagination: 61-70 Citation Subset: IM |
Affiliation:
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Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way, Oakland, CA 94609, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Cholesterol / metabolism Corticosterone / metabolism Female Fetus / enzymology* Gas Chromatography-Mass Spectrometry Male Mice Mutation Oxidoreductases Acting on CH-CH Group Donors / deficiency*, genetics, metabolism Pregnancy Progesterone / metabolism Smith-Lemli-Opitz Syndrome / enzymology*, genetics, metabolism Steroids / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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G0502165//Medical Research Council; R01 HD053036-05/HD/NICHD NIH HHS; R01HD053036/HD/NICHD NIH HHS; R01HL68660/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Steroids; 50-22-6/Corticosterone; 57-83-0/Progesterone; 57-88-5/Cholesterol; EC 1.3.-/Oxidoreductases Acting on CH-CH Group Donors; EC 1.3.1.21/7-dehydrocholesterol reductase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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