Glucocorticoids increase parathyroid hormone receptors in rat osteoblastic osteosarcoma cells (ROS 17/2).
Glucocorticoids increase parathyroid hormone receptors in rat osteoblastic osteosarcoma cells (ROS 17/2).
复制标题
糖皮质激素增加大鼠成骨细胞骨肉瘤细胞中的甲状旁腺激素受体 (ROS 17/2)。
DOI：
10.1002/jbmr.5650030617
复制
发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Segre,GV
中科院分区：
文献类型：
--
作者：
Yamamoto,I;PottsJr,JT;Segre,GV
使用具有成骨细胞表型的大鼠骨肉瘤衍生细胞（ROS 17/2）和[125 I][Nle 8，Nle 18，Tyr 34]牛（B）PTH-（1-34）酰胺作为放射性配体，研究了糖皮质激素对甲状旁腺激素（PTH）受体的影响。用生理浓度的氢化可的松处理细胞导致PTH结合的时间和剂量依赖性增加。暴露于氢化可的松（2 × 10− 7 M）10 h后可观察到PTH结合增加，48 h时最大程度增强，并在随后连续暴露于类固醇的7天内维持。随着氢化可的松的去除，PTH受体结合迅速恢复到对照水平。PTH结合的增加归因于受体结合位点的可用性增加，而不是受体结合亲和力的改变，并被放线菌酮阻断。PTH刺激的腺苷酸环化酶也被糖皮质激素增强，并且观察到PTH结合和PTH刺激的腺苷酸环化酶之间密切相关。然而，氢化可的松不仅增加了PTH结合，而且增强了受体后信号传导的效率：5′-鸟苷酰亚胺二磷酸[Gpp（NH）p]-和毛喉素刺激的腺苷酸环化酶活性也增加了。因此，增强甲状旁腺素刺激腺苷酸环化酶的糖皮质激素导致至少两个效果增加受体的可用性和增强受体后效率的跨膜信号。
The effects of glucocorticoids on parathyroid hormone (PTH) receptors was studied using rat osteosarcoma‐derived cells (ROS 17/2), which have an osteoblastic phenotype, and [125I][Nle8, Nle18, Tyr34]bovine(b)PTH‐(1–34)amide as the radioligand. Treatment of cells with physiologic concentrations of hydrocortisone resulted in a time and dose‐dependent increase in PTH binding. The increase in PTH binding could be observed by 10 h of exposure to hydrocortisone (2 × 10−7M), was maximally enhanced by 48 h, and was maintained for the subsequent 7 days of continuous exposure to the steroid. With removal of hydrocortisone, PTH receptor binding promptly returned toward control levels. The increase in PTH binding was attributed to an increase in the availability of receptor binding sites, not to altered receptor binding affinity, and was blocked by cycloheximide. PTH‐stimulated adenylate cyclase was also enhanced by glucocorticoids, and a close correlation was observed between PTH binding and PTH‐stimulated adenylate cyclase. However, hydrocortisone not only increased PTH binding but also enhanced the efficiency of postreceptor signaling: 5′‐guanylimidodiphosphate [Gpp(NH)p]‐ and forskolin‐stimulated adenylate cyclase activities were also increased. Thus, enhanced PTH stimulation of adenylate cyclase by glucocorticoids resulted from at least two effects—increased receptor availability and enhanced postreceptor efficiency of transmembranous signaling.