Klein R F, Nissenson R A, Strewler G J
Endocrine Unit, Veterans Administration Medical Center, San Francisco, CA.
Bone Miner. 1988 Jul;4(3):247-56.
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.
甲状旁腺激素（PTH）和降钙素可刺激骨腺苷酸环化酶活性并增加骨cAMP含量，但PTH增强而降钙素抑制骨吸收。本研究检测了腺苷酸环化酶的非激素激活剂福斯可林对19日龄胎鼠四肢骨骨吸收和cAMP积累的影响。福斯可林（10^(-9)至10^(-5) M）以浓度依赖的方式刺激骨cAMP生成。然而，与同样刺激cAMP积累的bPTH(1-34)不同，福斯可林不刺激骨吸收。此外，尽管福斯可林增强了PTH对骨cAMP水平的刺激作用，但它并未增强PTH的骨吸收活性。相反，高剂量的福斯可林（10^(-6)至10^(-5) M）表现出类似降钙素的作用，可抑制PTH介导的骨吸收。这些结果支持cAMP的第二信使功能介导降钙素的抑制作用，但不介导PTH对骨吸收的刺激作用。
