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Glucocorticoids increase parathyroid hormone receptors in rat osteoblastic osteosarcoma cells (ROS 17/2)
Author(s) -
Yamamoto Itsuo,
Potts John T.,
Segre Gino V.
Publication year - 1988
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650030617
Subject(s) - parathyroid hormone , cyclase , medicine , endocrinology , adenylate kinase , forskolin , receptor , parathyroid hormone receptor , chemistry , cycloheximide , stimulation , osteoblast , biology , calcium , hormone receptor , in vitro , biochemistry , protein biosynthesis , cancer , breast cancer
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 [ 125 I][Nle 8 , Nle 18 , Tyr 34 ]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 −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.