REGULATION OF RAT MYOSIN HEAVY CHAIN GENE EXPRESSION BY THYROID HORMONE.

Persistent Link:
http://hdl.handle.net/10150/184004
Title:
REGULATION OF RAT MYOSIN HEAVY CHAIN GENE EXPRESSION BY THYROID HORMONE.
Author:
GUSTAFSON, THOMAS A.
Issue Date:
1987
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:
Myosin heavy chain (MHC) isoforms in vertebrate striated muscles are encoded by a highly conserved multigene family. Seven sarcomeric MHCs are known to be expressed in cardiac and skeletal muscles of the rat. These isoforms show distinct patterns of tissue-specific expression which are hormonally and developmentally regulated. Thyroid hormone has been shown to regulate the expression of the ventricular isoforms by causing an accumulation of alpha-MHC and a repression of beta-MHC. Alterations in thyroid status have also been reported to affect MHC isoforms in skeletal muscles. The first part of this study describes the development of a dot-blot assay with which to measure the levels of the sarcomeric MHC mRNAs. This assay was utilized in part two of this dissertation to analyze the effects of thyroid hormone administration on the expression of MHC and actin mRNAs in ventricular muscle, as well as in representative fast and slow skeletal muscles of the hypothyroid rat. The results indicate that expression of all of the MHC genes is regulated by thyroid hormone in a highly complex, tissue specific manner. Also, thyroid hormone caused transient increases in the expression of cardiac actin mRNA in the ventricle, but no actin isoform transitions were observed in any muscle type. The third portion of this dissertation describes the development of a cultured cell system that has been used to analyze changes in MHC and alpha-actin gene expression in response to thyroid hormone in vitro. Cultured primary fetal cardiomyocytes were found to express only the cardiac MHC and actin isoforms. In addition, the alpha- and beta-MHC isoforms were found to be regulated by thyroid hormone in a similar manner to that observed in the intact rat ventricle. In the final portion of this study, the promoter region of the thyroid hormone inducible gene, alpha-MHC, was isolated and ligated to the bacterial chloramphenicol acetyltransferase gene. Chimeric genes were utilized in transfection studies and found to be thyroid hormone inducible. The results suggest that DNA sequences in the 5' flanking region of the alpha-MHC gene are sufficient to mediate hormone induction of the gene.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Thyroid hormones.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Morkin, Eugene

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleREGULATION OF RAT MYOSIN HEAVY CHAIN GENE EXPRESSION BY THYROID HORMONE.en_US
dc.creatorGUSTAFSON, THOMAS A.en_US
dc.contributor.authorGUSTAFSON, THOMAS A.en_US
dc.date.issued1987en_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.abstractMyosin heavy chain (MHC) isoforms in vertebrate striated muscles are encoded by a highly conserved multigene family. Seven sarcomeric MHCs are known to be expressed in cardiac and skeletal muscles of the rat. These isoforms show distinct patterns of tissue-specific expression which are hormonally and developmentally regulated. Thyroid hormone has been shown to regulate the expression of the ventricular isoforms by causing an accumulation of alpha-MHC and a repression of beta-MHC. Alterations in thyroid status have also been reported to affect MHC isoforms in skeletal muscles. The first part of this study describes the development of a dot-blot assay with which to measure the levels of the sarcomeric MHC mRNAs. This assay was utilized in part two of this dissertation to analyze the effects of thyroid hormone administration on the expression of MHC and actin mRNAs in ventricular muscle, as well as in representative fast and slow skeletal muscles of the hypothyroid rat. The results indicate that expression of all of the MHC genes is regulated by thyroid hormone in a highly complex, tissue specific manner. Also, thyroid hormone caused transient increases in the expression of cardiac actin mRNA in the ventricle, but no actin isoform transitions were observed in any muscle type. The third portion of this dissertation describes the development of a cultured cell system that has been used to analyze changes in MHC and alpha-actin gene expression in response to thyroid hormone in vitro. Cultured primary fetal cardiomyocytes were found to express only the cardiac MHC and actin isoforms. In addition, the alpha- and beta-MHC isoforms were found to be regulated by thyroid hormone in a similar manner to that observed in the intact rat ventricle. In the final portion of this study, the promoter region of the thyroid hormone inducible gene, alpha-MHC, was isolated and ligated to the bacterial chloramphenicol acetyltransferase gene. Chimeric genes were utilized in transfection studies and found to be thyroid hormone inducible. The results suggest that DNA sequences in the 5' flanking region of the alpha-MHC gene are sufficient to mediate hormone induction of the gene.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectThyroid hormones.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMorkin, Eugeneen_US
dc.identifier.proquest8709893en_US
dc.identifier.oclc698372328en_US
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