Abstract

Continuous administration of estrogens for 7-9 months, both steroidal and nonsteroidal, to male BALB/c mice, leads to the formation of testicular Leydig cell tumors. Three days following the subcutaneous implantation of a pellet of estrogen in cholesterol, there is a peak in the incorporation of 3H-tymidine into the DNA of the interstitial cells. These effects are hypothesized to be mediated by the estrogen receptor system in the Leydig cell. Common experimental techniques for the measurement of hormone binding, such as dextran coated charcoal treatment, proved to be impossible to employ in this system, therefore a procedure was developed using hydroxyapatite to obtain binding data. The cytosolic estrogen receptor was found to have a dissociation constant for estradiol-17β of 6.5 x 10-8 M, while that of the nuclear estrogen receptor was 1.25 x 10-8 M. Competition assays were utilized to determine the cytosolic estrogen receptor's affinity for nonsteroidal estrogens, steroidal estrogens, and triphenyletylene.

The estrogen mediate their cellular activities through a specific protein known as an estrogen receptor. Estrogen binding to this protein, whether first in the cytoplasm followed by translocation of this complex to the nucleus, or initially in the nucleus where it interacts with the chromatin of the target cell, causes an immediate raise in RNA production (Jensen, 1965.). This RNA production eventually results in the production of cellular proteins required for cell proliferation. Induction of a neoplasm in response to estrogen may involve this pathway of action. Elucidation of estrogen action on the testes of BALB/c mice began with the examination of this receptor system.

The first concept of a receptor was formulated by Langley (1878) when he described the effects of atropine and pilocarpne on salivary flow in cats. In 1905 Langley theorized the existence of what he called "a receptive substance" involved in the interaction of nicotine and curare with muscle. He also postulated that this type of interaction was applicable to adrenaline, thyroid hormone, and secretin.

The term "hormone" was introduced by Starling (1905) meaning to excite or arouse. Starling recognized that hormones traveled through the blood stream to their target organs, and that the body produced them according to physiological needs. A quantitative basis for the receptor nuclei and stimulated the incorporation of 3H-thymidine. Thus only those substance that provoked a complete estrogen receptor response were observed to stimulate DNA synthesis in mouse testicular Leydig cells.

LLU Discipline

Biochemistry

Department

Biochemistry

School

Graduate School

First Advisor

R. Bruce Wilcox

Second Advisor

W. Barton Rippon

Third Advisor

Barry L. Taylor

Fourth Advisor

E. Clifford Herrmann

Fifth Advisor

Daila S. Gridley

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1986

Date (Title Page)

6-1986

Language

English

Library of Congress/MESH Subject Headings

Leydig Cell Tumor; Receptors, Estrogen; Testicular Neoplasms

Type

Dissertation

Page Count

ix; 237

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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