Corticotropin-releasing factor up-regulates its own receptor gene expression in corticotropic adenoma cells in vitro.

To investigate the expression of CRF receptor (CRF-R) in human corticotropic adenoma (hCA) cells, we analyzed messenger RNA (mRNA) levels of type-1 GRF-R (CRF-R1). Adenomas were obtained from 10 patients with Cushing's disease. Northern blot analysis using a rat GRF-R1 complementary RNA probe revealed a main hybridization band of 2.7 kilobases in all the hCAs. The GRF-R1 mRNA level significantly increased after 1 h, reached 15-fold the basal level at 8 h, and remained elevated 24 h after the addition of 10 nmol/L GRF in vitro. Dose dependency of the stimulatory effect of CRF was also demonstrated in hCA cells, whereas CRF down-regulated CRF-R1 mRNA levels in rat anterior pituitary (AP) cells. Treatment with dexamethasone or vasopressin decreased the CRF-R1 mRNA level in hCA cells, as observed in rat AP cells. In conclusion, we detected CRF-R1 mRNA in all hCAs tested. The GRF-R1 mRNA level was up-regulated by GRF itself in cultured hCA cells, in contrast to the down-regulation in rat AP cells.