Abstract

Fetal rat lung (FRL) cells incubated in the presence of retinoic acid or dexamethasone exhibit altered 125I-epidermal growth factor (EOF) binding capacity. Retinoic acid enhances 125I-EGF binding 3-fold following 24 hours of 37° incubation. In contrast, FRL cells incubated in the presence of dexamethasone display a 2-fold reduction in 125I-EGF binding capacity. The change in binding capacity, induced by either hormone, was due to alterations in the average number of receptors per cell as determined by Scatchard analysis of 125I-EGF binding. In the absence of retinoic acid or dexamethasone, FRL cells were calculated to have approximately 27,000 receptors per cell, while cell treated with retinoic acid or dexamethasone have, respectively, 72,000 or 16,000 receptors per cell. Immunoprecipitation of EGF receptor protein metabolically labeled with 35S-methionine demonstrated that both hormones alter EGF receptor synthesis and the level of total EGF receptor protein.

To study the mechanisms used by these hormones to alter receptor metabolism, I analyzed the effects of the hormones on 125I-EGF binding capacity and receptor synthesis in the presence and absences of inhibitors of translation (cycloheximide) and transcription (actinomycin D). These results indicated that both agents modified 125I-EGF binding and receptor synthesis by regulating the level of specific mRNAs. Unlike dexamethasone, retinoic acid appears to regulate EGF receptor mRNA indirectly, suggesting that, in FRL cells, retinoic acid may regulate EGF receptor synthesis through the synthesis of an intermediate molecule, possibly a transcription factor.

Though the potential significance of EGF receptor regulation to hormone responsiveness seems obvious it is more difficult to demonstrate. A correlation between EGF receptors regulation and EGF-induced growth demonstrated, although, only during log phase growth. The most striking observation that could be related to increased receptor protein, however, was that retinoic acid treatment synergistically enhanced EGF-stimulated PGE2 secretion over 6-fold.This finding may indicate a physiologically significant effect of EGF receptor regulation in these cells.

LLU Discipline

Anatomy

Department

Anatomy

School

Graduate School

First Advisor

Graham Carpenter

Second Advisor

Paul J. McMillan

Third Advisor

P. Ben Nava

Fourth Advisor

William Fletcher

Fifth Advisor

Robert Teel

Sixth Advisor

Bruce Wilcox

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1989

Date (Title Page)

6-1989

Language

English

Library of Congress/MESH Subject Headings

Vitamin A; Dexamethasone; Growth Substances; Receptors, Endogenous Substances -- physiology

Type

Dissertation

Page Count

x; 136

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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