Defense Date

1980

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Dentistry

First Advisor

Joseph P. Liberti

Abstract

The in vivo regulation of several acid hydrolases by growth hormone was investigated in an attempt to lend insight into the mechanism of growth hormone action. In addition, the relationship of these enzymes to age-dependent changes in skeletal growth rate was examined. Initial studies showed that hypophysectomy reduced the activity of an unknown cartilage protease, which was assayed by digestion of gelatin-membrane substrates at pH 4.0. Treatment of hypophysectomized rats with growth hormone enhanced this activity to about normal levels. The unidentified protease activity was also shown to be higher in younger, more rapidly growing rats, than in older, less rapidly growing rats. These observations suggested that one or more lysosomal, acid proteases, called cathepsins, may be related to skeletal growth. Therefore, the relationship between three known lysosomal enzymes, namely cathepsin D, cathepsin B and acid phosphatase, and cartilage growth rate was examined. Cartilage cathepsin D and acid phosphatase activities of hypophysectomized rats were reduced relative to normal controls. Treatment of hypophysectomized rats with growth hormone enhanced these two enzyme activities towards normal levels. Pepstatin titration experiments suggested that the elevated cartilage cathepsin D activity corresponded to an increased enzyme concentration. Cartilage cathepsin B activity was refractory to hypophysectomy and growth hormone-treatment. The cartilage activity of all three enzymes was much greater in younger, more rapidly growing normal animals, than in older, less rapidly growing normal animals. Apparently, this was a result of decreased cell number and enzyme concentration. The growth rate and cartilage acid hydrolase activities of hypophysectomized animals varied minimally with increasing rat age. The enzyme modulations cited could be, at least in part, tissue specific as liver acid hydrolase activities did not parallel growth hormone and age-dependent growth rate. Overall, these results suggest that cartilage cathepsin D and acid phosphatase activities are coordinately controlled and related to skeletal growth rate. Taken together with other studies relating acid hydrolases to tissue growth, these observations stimulate speculation that the mechanism of growth hormone action and, derivatively, skeletal growth in general may occur via acid hydrolase-mediated processes.

Comments

Scanned, with permission from the author, from the original print version, which resides in University Archives.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

9-27-2017

Included in

Dentistry Commons

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