Dexamethasone regulates somatostatin receptor subtype messenger ribonucleic acid expression in rat pituitary GH4C1 cells.
Ligand binding studies have shown that glucocorticoids down-regulate somatostatin receptor (sst) concentration in several endocrine target cells and cell lines including GH4C1 cells. However, it has not been determined whether this decrease in sst number occurred via transcriptional and/or posttranscriptional events. In the present study, we have investigated the effect of dexamethasone (Dex) treatment (1 microM) of GH4C1 cells for up to 48 h on the steady state level of messenger RNA (mRNA) for sst1, sst2, and sst3, the predominant isoforms expressed in this cell line, by solution hybridization-nuclease protection analysis. Exposure of GH4C1 cells to Dex for 2 h increased sst1 mRNA levels 2.5-fold and sst2 1.5-fold compared with controls (Con). Prolonged exposure, however, resulted in a decrease in mRNA levels of sst1 to 50% and sst2 to 30% of Con by 24-48 h. In contrast, sst3 mRNA levels were unchanged at 2 h, decreased to 30% of Con by 6 h, and remained decreased for up to 24 h. Longer exposure resulted in a dramatic increase in expression, reaching 350% of Con by 48 h. The Dex effect on expression of all subtypes was dose dependent, maximal at 10 nM. Steroid hormone regulation of sst mRNA expression in GH4C1 cells proved to be complex. Exposure to Dex for 24 h, as expected, decreased expression of all subtypes. Progesterone, however, increased sst1 mRNA levels, decreased sst3 levels, but was without effect on sst2; treatment with estrogen and testosterone increased expression of all three subtypes. Nuclear run-on assays indicated that the Dex-induced changes in sst1 and sst2 mRNA levels were associated with congruent changes in the transcription rate of sst genes. Thus, glucocorticoids regulate sst expression in GH4C1 cells, at least in part, by controlling the rate of transcription of sst genes.
Xu
Y
Y
Department of Medicine, State University of New York at Stony Brook 11794, USA.
Berelowitz
M
M
Bruno
J F
JF
D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004967:Estrogens / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007700:Kinetics; D010902:Pituitary Gland / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017481:Receptors, Somatostatin / Q000235:genetics*; D013739:Testosterone / Q000494:pharmacology; D014158:Transcription, Genetic
D004967:Estrogens; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013739:Testosterone; D011374:Progesterone; D003907:Dexamethasone