Abstract

A deleterious effect of spaceflight on human health is the loss of bone associated with the prolonged lack of gravitational stress on the skeleton. A potential for bone loss is indicated by the hypercalciuria and decreased heel bone density determined in Skylab astronauts. Histological studies of juvenile laboratory rats in actual spaceflight and in simulation models document a suppression of bone formation with little alteration of bone resorption. The mechanism for net bone loss needs to be defined in order to develop measures for its prevention or correction.

Skeletal growth factors, which may mediate coupling and locally regulate bone volume by regulating coupling, have been isolated from human and bovine bones. The purpose of this study was to investigate whether a deficit in circulating levels of a skeletal growth factor, Insulin-like Growth Factor-II, could be correlated to the suppression in bone formation documented in rats during simulated weightlessness. This question was approached by using a radioreceptor assay of Mohan et al (1988) - specific for the measurement of human IGF-II - to measure circulating levels of an IGF-II-like protein in the rat.

A protein extracted from rat bone was capable of displacing 125I-iodo-hIGF-II in parallel to hIGF-ll standard in an RRA. This rat IGF-ll-like activity (rIGF-ll) was partially isolated from rat bone. This partially purified rIGF-ll activity was sensitive to proteolytic and reducing conditions and stable at temperatures up to 75°C.

With the availability of an IGF-II RRA for rat serum, an in vivo experiment to test the hypothesis was conducted using the rat model of skeletal unloading (tail-traction suspension). This model simulates certain effects of weightlessness on bone volume through the skeletal unloading of the hind limbs. Osteopenia was induced in rats by the tail-traction model. This alteration in bone turnover was correlated to significantly reduced levels of circulating rIGF-ll.

A measured deficit in serum rIGF-ll levels in neurotomized rats supported the observation in the tail-traction model. These results culminated in a publishable manuscript which is the first report of a change in serum levels of a growth factor associated with an alteration in skeletal loading.

LLU Discipline

Biochemistry

Department

Biochemistry

School

Graduate School

First Advisor

Thomas A. Linkhart

Second Advisor

George M. Lessard

Third Advisor

R. Bruce Wilcox

Fourth Advisor

Terry D. Shultz

Fifth Advisor

S. Mohan

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1988

Date (Title Page)

9-1988

Language

English

Library of Congress/MESH Subject Headings

Bone and Bones -- abnormalities; Weightlessness; Growth Substances

Type

Dissertation

Page Count

vii; 118

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

Download

Share

COinS