Dexamethasone increases and serum decreases growth hormone receptor binding to UMR-106.01 rat osteosarcoma cells.
Dexamethasone (DEX) is known to exert major effects on functions of osteoblast-like cells. We investigated its action on the regulation of GH receptors in the osteoblast-like osteosarcoma cells UMR-106.01. DEX stimulated [125I]human GH (hGH) binding to UMR-106.01 cells. This effect was dose dependent and significant in a concentration range of 10(-8)-10(-6) M. The maximum effect was an increase of 42 +/- 1.4% (n = 3; mean +/- SE) above control, P < 0.01, at 10(-7) M DEX. Time dependence of this stimulation was observed, with a peak between the 12th and the 16th h of incubation, an effect being still detectable at 48 h. Cycloheximide decreased [125I]hGH binding and completely abolished the stimulating effect of DEX, suggesting that modulation of [125I]hGH binding by DEX is fully dependent on protein synthesis. Addition of fetal calf serum (FCS) resulted in a dose-dependent decrease of [125I]hGH binding to 24 +/- 2% of control (n = 3; mean +/- SE), P < 0.001, without interfering with the stimulatory effect of DEX, the ratio of DEX vs. control being higher with increasing FCS doses. Taken together, these results suggest the existence of different pathways for the regulation of GH receptor binding to UMR-106.01 cells, including a stimulatory one at the pretranslational level for DEX and an inhibitory one for (growth) factors present in FCS.
Salles
J P
JP
Department of Endocrinology, Free University Hospital, Amsterdam, the Netherlands.
De Vries
C P
CP
Netelenbos
J C
JC
Slootweg
M C
MC
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005312:Fetal Blood / Q000502:physiology*; D013006:Growth Hormone / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism*; D051381:Rats; D011986:Receptors, Somatotropin / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D011986:Receptors, Somatotropin; D003907:Dexamethasone; D013006:Growth Hormone; D003513:Cycloheximide