Glucocorticoids increase parathyroid hormone receptors in rat osteoblastic osteosarcoma cells (ROS 17/2).
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 x 10(-7) M), 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.
Yamamoto
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Department of Nuclear Medicine and Radiology, Kyoto University School of Medicine, Japan.
Potts
J T
JT
Segre
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GV
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002999:Clone Cells; D000242:Cyclic AMP / Q000096:biosynthesis; D003513:Cycloheximide / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology*; D010006:Osteoblasts / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D003513:Cycloheximide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006854:Hydrocortisone