Hydroxyproline Excreted in the Urine: Its Source from Collagen of Tissues After14C-Proline in Rats with and Without Administration of Prednisone1

Abstract

To obtain more direct evidence that a considerable part of as much as 80% reduction in urinary hydroxyproline produced by administration of prednisone comes from insoluble collagen, specific activities of urinary hydroxyproline were determined in young rats and guinea pigs up to 28 and 35 days, respectively, after administration of ¹⁴C-proline. The findings of Prockop are confirmed that the specific activities of urinary hydroxyproline after 28 days are about ⅔ that of insoluble collagen of the tissues in control rats without prednisone. In guinea pigs the specific activities of urinary hydroxyproline after 35 days were also found to be about ⅔ that of insoluble collagen in the tissues. After 2 mg/100 g body wt of prednisone injected intraperitoneally in rats on alternate days for 10 days, the ratio of hydroxyproline specific activities in urine to those of insoluble collagen in the tissues remained at about two-thirds, in spite of the large reduction in both body weight and urinary hydroxyproline. Apparently the rate of degradation of insoluble collagen in the tissues was reduced sufficiently to permit the ratio to remain the same. We did not analyze the amounts of dialyzable and nondialyzable ¹⁴C-hydroxyproline-containing peptides in the urine to evaluate this point more fully. Unfortunately these experiments cannot be done now since the laboratory has been closed. Another effect of prednisone that takes place immediately after the first injection is an increase in the specific activities of urinary hydroxyproline, which lasts about 1 day. This would be more reasonable if nascent collagen hydroxyproline instead of soluble collagen is degraded and is excreted in the urine during the early synthesis of collagen after administration of ¹⁴C-proline. On the first day of prednisone (18 days after ¹⁴C-proline), collagen is synthesized from nonradioactive proline, and a decrease in collagen synthesis appears as an increase in radioactivity in the curves. Data in tissues and urine for 1 hr to many days in rats and guinea pigs are discussed, and apparently indicate that excretion of nascent collagen hydroxyproline in urine would be more consistent with the results than excretion from soluble collagen in the tissues.