Date of Award

1970

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Pharmaceutical Sciences

First Advisor

George C. Fuller

Abstract

The biochemical mechanism by which glucocorticoids affect collagen metabolism was investigated. Triamcinolone, hydrocortisone and methylprednisolone significantly decreased liver proline hydroxylase activity in vivo. This was not a manifestation of an antianabolic effect on protein. Triamcinolone inhibited liver proline hydroxylase activity in a dose dependent manner in vivo. An observed elevation of liver hydroxylase activity in adrenalectomized animals was decreased to control level by hydrocortisone treatment.

Subdermal implants of three types of sponges (polyurethane, cellulose and polyvinyl) were used to induce granuloma growth as a model system of inflammation. The anti-inflammatory activity of corticosteroids was correlated with inhibition of proline hydroxylase activity in granuloma tissue.

The data indicate that corticosteroids decrease collagen synthesis by inhibiting the rate limiting enzyme. This inhibitory effect on collagen metabolism is correlated with observed anti-inflammatory activity.

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