Studies on Intravenously Infused Dexamethasone in Sheep

Abstract

Aust. J. Bioi. Sci., 1978, 31, 373-83 The metabolism of [1,2(n)-3Hldexamethasone intravenously infused for periods of 4 and S days was examined in four Merino wethers.On average 85·6±2·8 (s.e.m.) % of the total dose was recovered, 56·2±5·1 and 29·4±3·3% being excreted in urine and faeces respectively. In total 12·4 % of the dose was associated with the unconjugated steroid fraction which represented 22% of the total urinary radioactivity.Thin layer chromatography of the urinary unconjugated fractlon revealed, apart from dexamethasone, five major and three minor radioactive components designated as I, III, IV, V, VIII and II, VII, IX respectively. Approximately 83 % of the radioactivity associated with the unconjugated fractions was found in constituents more polar than dexamethasone with the radioactivity mainly confined to the principal metabolite IV, Rc = 0·24 (dexamethasone, Rc = 0·45;'cbloroform: formarnide 50:1). The urinary constituent VI, Rc = 0·37, was detected only -during-the second half of the 8-day infusion with the peak of excretion on day 6.During the first 30 h of [3Hldexamethasone administration the plasma radioactivity reached the level which remained relatively constant throughout the infusions. The initial high level of radioactivity detected in the plasma unconjugated fraction as well as dexamethasone during the first 24 h infusion declined over the next 2 days; this was followed by a small increase during the final period of infusions.The radioactivity of the plasma unconjugated fraction was distributed, apart from dexamethasone, into six constituents (I, III, IV, V, VIII and IX) which when analysed by thin layer chromatography appeared to be qualitatively similar to those found in urine.These results led to the conclusion that one or more products of dexamethasone metabolism might be biologically active and thus potentially important in inhibiting wool fibre growth in sheep.

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

“…The dexamethasone concentration profiles revealed a pattern which reflects the extensive dexamethasone metabolism as shown by Leish and Panaretto (1978). Also, the fall in the wet skin weight per unit area confirmed previous observations in sheep (Panaretto, unpublished data) and studies in rats (Young et al 1977;Cutroneo and Counts 1975) in which the similar weight loss has been shown on drying the dexamethasone-treated wet skin to constant weight.…”

“…Administration of several glucocorticoids to sheep and the resultant inhibition of growth of wool fibres have been well documented (Panaretto and Wallace 1978a, 1978b, 1979Leish and Panaretto 1978). In ,order to induce shedding of the majority of wool fibres, it was found necessary to maintain elevated glucocorticoid concentrations in the plasma of sheep over 8 days or longer (Panaretto 1979).…”

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

“…The concentration profiles for dexamethasone here were similar to those of Panaretto and Wallace (1978b). Leish and Panaretto (1978) reported similar concentration patterns using [3H]dexamethasone. The peaks in steroid concentration have not been investigated here.…”

Comparisons of the Plasma Steroid Concentration Profiles and Wool Growth Responses After Administration of Two Forms of Dexamethasone to Sheep

“…Dexamethasone quickly disappeared from the circulation on cessation of the infusion (Leish and Panaretto 1978) and by 45 days after treatment wool growth was almost restored. to normal.…”

“…Previous papers have described some effects of different forms of dexamethasone (Panaretto et al 1975;Panaretto and Wallace 1978a; Leish and Panaretto 1978) and flumethasone Wallace 1978b, 1979) on wool growth in Merino sheep. The results have shown that these steroids induce fibre shedding.…”