Corticosteroid-induced changes in the responsiveness of human osteoblast-like cells to parathyroid hormone.
We investigated the in vitro effect of corticosteroids on the responsiveness of human cells of osteoblast lineage to parathyroid hormone (PTH). Prior to corticosteroid treatment, the cells demonstrated only a small increase in cAMP production and no measurable change in transmembrane potential in response to PTH. Exposure of cells to dexamethasone resulted in a 5-fold increase in PTH-induced cAMP production and in measurable PTH-induced membrane depolarization in all cells studied. The effect of corticosteroids on cAMP production was specific for PTH (not seen with PGE1 or forskolin), occurred in a time- and dose-dependent fashion and in the absence of cell proliferation. Most of the cells were of osteoblast lineage as determined by the presence of alkaline phosphatase activity and BGP secretion. These findings further support the idea that corticosteroids increase the sensitivity of cells of osteoblast lineage to PTH, perhaps by transforming cells which initially have a low responsiveness to PTH to a state of high responsiveness.
Silve
C
C
Laboratoire du Calcium et Tissu Osseux dans l'Organisme en Développement, CNRS UA.583, Hôpital des Enfants-Malades, Paris, France.
Fritsch
J
J
Grosse
B
B
Tau
C
C
Edelman
A
A
Delmas
P
P
Balsan
S
S
Garabedian
M
M
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D001706:Biopsy; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002648:Child; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010641:Phenotype
D000305:Adrenal Cortex Hormones; D010281:Parathyroid Hormone; D000242:Cyclic AMP