Effect of Intravenously Infused Dexamethasone on Collagen Metabolism in Skin of Merino Sheep

Abstract

The effects of an 8-day intravenous infusion of dexamethasone (7·6 mg kg-o . 75 body weight) on collagen biosynthes's and wool growth in skin were examined in four Merino wethers.Plasma dexamethasone concentrations reached their peaks during the first 24 h infusion, which were followed by relatively stable levels (c. 1 x 10-7 M) for the next 4-5 days. Minor increases in plasma dexamethasone levels were recorded during the final 2 days of treatment. Dexamethasone concentrations quickly fell below the level of detection once infusion ceased.Marked decreases in the wet weight, thickness and protein content of skin were observed at the end of infusion. DNA content was reduced to 42·4±4·9 % s.e.m. during the first 2 days of treatment, but in the next 4 days of infusion gradually increased to 85·0±12·5% of controls. The level of collagen (expressed as hydroxyproline content of its acid hydrolysate) was elevated throughout the infusion and then gradually declined in 3 weeks to about 60 % of controls.The biosynthesis of collagen measured by the rate of [14C]hydroxyproline formation and the activity of proline, 2-oxoglutarate dioxygenase (EC 1.14.11.2, formerly prolyl hydroxylase) was reduced during the first half of treatment to a greater extent than the rate of [14C]proline incorporation into proteins.Wool growth was reduced by 80·4 ± 11 ·6% in the post-infusion period which allowed three sheep out of four to be defleeced.Inhibition of collagen biosynthesis in sheep skin was due initially to a decrease in the activity of proline, 2-oxoglutarate dioxygenase and later to the reduced rate of proline incorporation into proteins. It ,was also evident that changes in biosynthetic rate of collagen were not reflected in the total level of skin collagen. The extent of wool growth depression in individual animals paralleled the changes in DNA content and the extent of collagen biosynthesis inhibition.

Some Effects of Dexamethasone on Nucleic Acid Metabolism in Skin of Merino Sheep

“…It was highly probable that this was the case in the present experiments and the effects of steroid treatment on precursor incorporation were principally on the replicating cells in the follicle bulbs. The close correspondence in experiment 2 between the depression in mean wool growth (52 % of pretreatment value) and mean rate of precursor incorporation into DNA of skin (48 % of pretreatment values in the presence of excess thymidine) supported the suggestion that inhibitory glucocorticoid effects on wool follicles are mediated by a reduction in DNA synthetic rate (Leish and Panaretto 1979).…”

Effect of Dexamethasone and Cyclophosphamide on Urinary Hydroxyproline to Creatinine Ratios in Sheep

“…Dexamethasone infusion was thought to decrease or even prevent collagen degradation in the skin of sheep (Leish and Panaretto 1979) so that although there was a thinning of the skin in the sheep in the present experiment (unpublished data) catabolism of skin collagen should not have contributed to the increased output of urinary hydroxyproline. However, it is quite likely that at least some other hydroxyproline-containing tissues (Robins 1977) have also been affected.…”