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

We have previously demonstrated the presence of glucocorticoid receptors in bone cells and have suggested that direct inhibition of cell proliferation may contribute to glucocorticoid-induced osteoporosis. The present studies examine the issue of 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, we assessed the ability of dexamethasone to modulate the cAMP response to PTH. 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 -13 nM and half-maximal effects at -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. The data suggest that glucocorticoids may enhance cAMP-mediated PTH functions. (Endocrinology102: 589, 1978)