Glucocorticoid Potentiation of the Adenosine 3′,5′- Monophosphate Response to Parathyroid Hormone in Cultured Rat Bone Cells*

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Abstract
The presence of glucocorticoid receptors in bone cells was previously demonstrated. Direct inhibition of cell proliferation may contribute to glucocorticoid-induced osteoporosis. The present studies examine whether glucocorticoids might also alter bone status by interacting with parathyroid hormone (PTH) a major regulator of bone homeostasis. Since cyclic AMP (cAMP) is the putative mediator of PTH-induced inhibition of collagen synthesis as well as resorption, the ability of dexamethasone to modulate the cAMP response to PTH was assessed. Bone cells from calvaria of 20-21 day fetal rats were cultured for 6-7 days and the ability of PTH to stimulate cAMP was measured. The cells responded to both the synthetic (1-34) fragment and native PTH with a dose-dependent increase in cAMP. Dexamethasone treatment did not alter base-line levels of cAMP but did potentiate the cAMP response to PTH: 1- to 2-fold when assayed in the presence of theophylline and 2- to 4-fold in its absence. This potentiating effect could be detected only after a latent period of dexamethasone treatment and was proportional to the steroid exposure time. The effect was also glucocorticoid-specific and dose-dependent with maximal potentiation of cAMP being achieved at .apprx. 13 nM and half-maximal effects at .apprx. 1.3 nM dexamethasone. In part, the potentiation seemed to result from glucocorticoid inhibition of cAMP phosphodiesterase. Direct assay of phosphodiesterase revealed a dose-dependent decrease in activity after dexamethasone treatment. Glucocorticoids may enhance cAMP-mediated PTH functions.