The effect of cortisol on the adenosine 3',5'-monophosphate response to parathyroid hormone of bone in vitro.

Newborn rat calvariae, cultured for 24 h in the presence of cortisol (10(-6) M) have a cAMP response to parathyroid hormone (PTH) about twice as high as calvariae cultured in a control medium. This effect of cortisol is dose related; a maximal effect is evident at 10(-6) M, while none is detectable at 10(-9) M or less. With 10(-6) M estradiol, progesterone, or cholesterol, no effect on cAMP responsiveness is observed. This indicates that the effect observed with cortisol is specific. The effect of cortisol is more pronounced when isobutyl-methylxanthine (10(-4) M) is present during the subsequent incubation with PTH. Preincubation of the tissue with cortisol for 30 min before the addition of PTH has no effect. Similarly, when cortisol is added in conjunction with PTH, no effect is found. In no case did cortisol (10(-6) M) alter the time course of the PTH-induced cAMP effect when compared to the response of fresh calvariae. The results indicate that corticosteroids have an important function in maintaining cAMP responsiveness of bone to PTH in vitro.