Glucocorticoid regulation of 1,25(OH)2-vitamin D3 receptors in cultured mouse bone cells.

The ability of glucocorticoids to modulate 1,25(0H)2-Vitamin DS receptors was investigated in primary cultures of mouse osteoblast-like bone cells.We have previously shown that the concentration of receptors fluctuated during the culture cycle.High levels were found during log phase growth and low levels at confluence.Because of these dynamic changes in receptor concentration, the effects of glucocorticoids were examined throughout the culture cycle.During early log phase, dexamethasone (130 n ~) reduced both the concentration of receptors and the rate of [14C]thymidine incorporation to 60-70% of control levels.In late log phase, dexamethasone-treated cells transiently exhibited a higher receptor number than control cells.This relative increase in receptors appeared to result from a dexamethasone-mediated delay in reaching confluence and, therefore, a slower decline in receptors than exhibited by control cells.After confluence was attained, dexamethasone decreased the receptor content to the same extent as at the early log phase, but at this stage there was only a slight effect on [14C]thymidine incorporation and no change in DNA content.The dexamethasone inhibitory effects at both growth phases were shown to be dose-dependent, glucocorticoid-specific, and by Scatchard analysis to involve a selective change in receptor number without a change in receptor affinity.The relationship of the receptor level to the rate of cell proliferation was tested using epidermal growth factor, a hormone which promotes growth of these cells.In early log phase, epidermal growth factor blocked the inhibition of cell growth caused by dexamethasone and reversed the dexamethasone-mediated decline in receptor levels.The inhibitory effect of dexamethasone at confluence was found to be independent of its effects on cell proliferation.Chronic glucocorticoid therapy is associated with the development of osteopenia (1).Available data suggest that this process is multifactorial.We (2) and others (3,4) have shown that glucocorticoids directly inhibit bone cell replication and function.We have also demonstrated that glucocorticoids potentiate the action of parathyroid hormone on bone cells (5), a finding recently confirmed and extended by others (6-8).