Forskolin mimics the effects of calcitonin but not parathyroid hormone on bone resorption in vitro.

Parathyroid hormone (PTH) and calcitonin stimulate bone adenylate cyclase activity and increase bone cAMP content, but PTH enhances and calcitonin inhibits bone resorption. This study examined the effects of forskolin, a non-hormonal activator of adenylate cyclase, on bone resorption and cAMP accumulation in 19-day fetal rat limb bones. Forskolin (10(-9) to 10(-5) M) stimulated bone cAMP generation in a concentration-dependent manner. However, in contrast to bPTH(1-34), which also stimulated cAMP accumulation, forskolin did not stimulate bone resorption. Moreover, forskolin did not augment the bone-resorbing activity of PTH even though it potentiated PTH stimulation of bone cAMP levels. Rather, high doses of forskolin (10(-6) to 10(-5) M) exhibited a calcitonin-like effect to inhibit PTH-mediated bone resorption. These results support a second-messenger function of cAMP for the inhibitory effects of calcitonin, but not for the stimulatory effects of PTH on bone resorption.