Dexamethasone regulation of gastrin-releasing peptide receptor in human lung cells

We investigated the effects of the glucocorticoid, dexamethasone (Dex), on expression of the gastrin-releasing peptide (GRP) receptor by human small cell lung carcinoma (SCLC) SHP77 cells. After 12 h of 10 nM Dex exposure, a six-fold increase in the peak of GRP receptor mRNA compared with untreated controls (10.5 +/- 4 versus 1.65 +/- 0.15 attomols/mug total RNA, respectively, P < 0.05) occurred. GRP receptor mRNA levels fell to less than 0.5 attomots/mug total RNA after 24h; in Dex-treated cells, these levels rose to 1.2 compared with 0.12 attomots/mug total RNA in the absence of Dex after 7 days. A significant increase (P < 0.05) in the GRP receptor-specific binding was also found. Stimulation of SHP77 cell proliferation (25-35% in the presence of 10-100nM Dex; P < 0.0001) was observed after 4-8 days of exposure; this stimulation was inhibited by GRP receptor antagonists. SHP77 cell content and concentration of bombesin-Like peptides (BLP) in conditioned medium (approximately 4nM) was unchanged by Dex. Stimulation of human SCLC SHP77 cell proliferation by Dex may, in part, occur via effects on the GRP autocrine system in these cells. Published by Elsevier Ireland Ltd.