The effect of dietary manipulation on fetal and maternal cholesterol metabolism in the guinea pig.

Persistent Link:
http://hdl.handle.net/10150/185620
Title:
The effect of dietary manipulation on fetal and maternal cholesterol metabolism in the guinea pig.
Author:
Yount, Nannette Yquem.
Issue Date:
1991
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Diets consisting of non-purified guinea pig diet or non-purified guinea pig diet supplemented with either 1.1% of the bile acid binding resin cholestyramine or 0.25% cholesterol were fed to dams from the first day of conception. Whole body rates of endogenous cholesterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA levels were determined at 0, 40 and 60 days of gestation in the dam and fetus. Sterol synthesis studies indicated that maternal hepatic cholesterol synthesis was reduced 87% by dietary cholesterol and was increased 2.9-fold with cholestyramine feeding. The pattern of fetal hepatic and peripheral tissue cholesterol synthesis rates during development indicated that synthesis was highest at 40 days gestation, and by 60 days was reduced to levels similar to that found in the adult. Cholesterol synthesis rates in the fetus were relatively insensitive to dietary manipulation; however, maternal cholestyramine treatment did result in a 1.4-fold increase in fetal carcass cholesterol synthesis at 60 days gestation. To determine whether regulation at the level of feedback suppression or induction of steady state RNA levels were also present in the fetal organism, mRNA levels for HMG-CoA reductase were quantified in the maternal and fetal liver. In these studies the guinea pig was shown to have two reductase mRNA species of 4.5 and 3.2 kb, similar to transcript sizes identified for the hamster, rat and Drosophila. Although nearly equimolar in the 40 day gestation fetus the 3.2 kb transcript predominated at 60 days. Dietary treatment had only minor effects on fetal reductase mRNA levels at 40 days gestation; however, at 60 days gestation, fetuses from cholestyramine-fed dams had elevated levels of reductase mRNA and fetuses from cholesterol fed dams had reduced levels of reductase mRNA. These studies indicate that maternal cholesterogenic systems maintain responsiveness to dietary regulation during pregnancy at both the level of sterol synthesis rates and HMG-CoA reductase mRNA levels. These findings also indicate that it is possible to influence those mechanisms which modulate cholesterol homeostasis prenatally. Further studies will be required to determine if such effects extend into the post-natal period and beyond.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Dissertations, Academic; Molecular biology; Nutrition.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Nutritional Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
McNamara, Donald J.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleThe effect of dietary manipulation on fetal and maternal cholesterol metabolism in the guinea pig.en_US
dc.creatorYount, Nannette Yquem.en_US
dc.contributor.authorYount, Nannette Yquem.en_US
dc.date.issued1991en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractDiets consisting of non-purified guinea pig diet or non-purified guinea pig diet supplemented with either 1.1% of the bile acid binding resin cholestyramine or 0.25% cholesterol were fed to dams from the first day of conception. Whole body rates of endogenous cholesterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA levels were determined at 0, 40 and 60 days of gestation in the dam and fetus. Sterol synthesis studies indicated that maternal hepatic cholesterol synthesis was reduced 87% by dietary cholesterol and was increased 2.9-fold with cholestyramine feeding. The pattern of fetal hepatic and peripheral tissue cholesterol synthesis rates during development indicated that synthesis was highest at 40 days gestation, and by 60 days was reduced to levels similar to that found in the adult. Cholesterol synthesis rates in the fetus were relatively insensitive to dietary manipulation; however, maternal cholestyramine treatment did result in a 1.4-fold increase in fetal carcass cholesterol synthesis at 60 days gestation. To determine whether regulation at the level of feedback suppression or induction of steady state RNA levels were also present in the fetal organism, mRNA levels for HMG-CoA reductase were quantified in the maternal and fetal liver. In these studies the guinea pig was shown to have two reductase mRNA species of 4.5 and 3.2 kb, similar to transcript sizes identified for the hamster, rat and Drosophila. Although nearly equimolar in the 40 day gestation fetus the 3.2 kb transcript predominated at 60 days. Dietary treatment had only minor effects on fetal reductase mRNA levels at 40 days gestation; however, at 60 days gestation, fetuses from cholestyramine-fed dams had elevated levels of reductase mRNA and fetuses from cholesterol fed dams had reduced levels of reductase mRNA. These studies indicate that maternal cholesterogenic systems maintain responsiveness to dietary regulation during pregnancy at both the level of sterol synthesis rates and HMG-CoA reductase mRNA levels. These findings also indicate that it is possible to influence those mechanisms which modulate cholesterol homeostasis prenatally. Further studies will be required to determine if such effects extend into the post-natal period and beyond.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectDissertations, Academicen_US
dc.subjectMolecular biologyen_US
dc.subjectNutrition.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineNutritional Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMcNamara, Donald J.en_US
dc.contributor.committeememberHendrix, Mary J. C.en_US
dc.contributor.committeememberBrannon, Patsy M.en_US
dc.contributor.committeememberOishi, Karen K.en_US
dc.contributor.committeememberLei, David-
dc.identifier.proquest9202091en_US
dc.identifier.oclc711793553en_US
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