Altered parathyroid hormone- or calcitonin-stimulated adenosine 3′,5′-monophosphate release by isolated perfused bone from glucocorticoid-treated rats

Abstract

The present studies were designed to examine in vivo effects of glucocorticoid on PTH-or calcitonin (CT)-stimulated adenosine 3',5'-monophosphate (cAMP) release from the isolated perfused bone of rat and to test whether the duration of glucocorticoid administration influenced such effects. We assessed the ability of acute (24 hour) or chronic (2 week) dexamethasone administration to modulate the cAMP response to 5 micrograms human PTH-(1-34) or 1 micrograms eel CT. Acute treatment with dexamethasone (1 mg/100 g body wt) increased the cAMP response to PTH, but decreased the response to CT. This enhanced effect on PTH-stimulated cAMP release was not apparent in the presence of phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX, ImM). In contrast, chronic dexamethasone treatment (0.2 mg daily for 2 weeks) led to a decrease in both PTH- and CT-stimulated cAMP release. Such impaired response of the dexamethasone-treated bones to PTH was also found in rats that underwent parathyroidectomy 24 hours before sacrifice. These data indicate that 1) the duration of glucocorticoid administration may influence the effect of PTH on bone and 2) glucocorticoid may decrease cAMP-mediated CT function, regardless of the duration of treatment.