Glucocorticoid stimulation of growth hormone messenger ribonucleic acid levels in GH3 cells is inhibited by calcium but not by somatostatin.
Aside from studies of a possible synergism between T3 and glucocorticoids in regulating GH mRNA, there have been few previous studies of the modulation by hormones and other factors of glucocorticoid hormone regulation of pituitary cell GH gene expression. We have employed a serum-free medium containing no exogenously added Ca2+ to investigate whether Ca2+ or somatostatin influences the stimulation by the synthetic glucocorticoid dexamethasone of GH mRNA levels in GH3 cells. Basal levels were slightly (less than or equal to 2-fold) stimulated by CaCl2 (0.4 mM). The stimulation by dexamethasone (100 nM) of GH mRNA in GH3 cells incubated in serum-free medium with or without Ca2+ was, respectively, 20- and 25-fold. Thus, under these experimental conditions, little effect of Ca2+ on regulation by dexamethasone was observed. To further reduce Ca2+ levels in the incubation medium, EGTA (20 microM) was added to chelate residual Ca2+. In some but not all experiments, EGTA treatment yielded a slight decrease in basal GH mRNA levels. Time-course experiments performed in the presence of EGTA showed that during incubation periods with dexamethasone that yielded a detectable stimulation of GH mRNA (2-4 days), Ca2+ (0.4 mM) inhibited the dexamethasone stimulation by 3- to 5-fold. Investigations of the dose-response relationship of the effect of dexamethasone on GH mRNA performed under the same conditions showed that at dexamethasone concentrations that yielded a significant stimulation of GH mRNA (10 nM or greater), Ca2+ (0.4 mM) inhibited the dexamethasone stimulation by about 2-fold. In contrast to the inhibitory effects of Ca2+ on the stimulation by dexamethasone of GH mRNA in the GH3 cells, somatostatin had no effect at any concentration tested (1-1000 nM) on dexamethasone regulation of this mRNA.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D013006:Growth Hormone / Q000235:genetics*; D007700:Kinetics; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*
D012333:RNA, Messenger; D013004:Somatostatin; D004533:Egtazic Acid; D003907:Dexamethasone; D013006:Growth Hormone; D002118:Calcium