CORTICOTROPIN-RELEASING FACTOR (CRF) AND GLUCOCORTICOIDS MODULATE THEEXPRESSION OF TYPE-1 CRF RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN RAT ANTERIOR-PITUITARY CELL-CULTURES

Previous studies involving radioreceptor and functional assays have sh own that CRF and glucocorticoids are able to modulate CRF receptors of the brain and anterior pituitary. In this study, we analyzed the effe cts of CRF, vasopressin (AVP), dexamethasone (DEX), and corticosterone on the regulation of CRF receptor (CRF-R1) messenger RNA (mRNA) level s in cultured rat anterior pituitary cells. CRF decreased CRF-R1 mRNA levels in a time- and concentration-dependent manner. In the presence of 10 nM CRF, CRF-R1 mRNA levels decreased within 1 h (to 65 +/- 3% of the control value; P < 0.01) with a maximal effect after 3 h (to 28 /- 1% of the control value; P < 0.001). The concentration dependence o f the inhibitory effect of CRF at 3 h correlated with that required fo r ACTH secretion (half-maximal at -0.03 nar). Treatment with a maximal (100 nM) dose of AVP or a submaximal (0.1 nM) dose of CRF for 3 h red uced CRF-R1 mRNA levels to 66 +/- 3% and 53 +/- 6% of the control valu e, respectively. In the presence of both AVP and CRF, CRF-R1 mRNA leve ls were 32 +/- 3% of the control value. The incubation of cells for 3 h with 10 mu M forskolin to activate adenylate cyclase or with 20 nM 1 2-O-tetradecanoylphorbol-13-acetate to activate protein kinase C resul ted in a decrease in receptor mRNA levels to 40 +/- 9% (P < 0.01) and 28 +/- 8% (P < 0.001) of the control value, respectively, suggesting t hat the effects of CRF and AVP may be mediated by these pathways. DEX (20nM) also caused a dose- and time-dependent decrease in mRNA levels. Maximal inhibition was observed after 3 h (to 31 +/- 6% of the contro l value; P < 0.001), with a partial recovery of mRNA levels at 24 or 4 8 h. Corticosterone similarly inhibited the accumulation of CRF-R1 mRN A in a dose- and time-dependent manner, but, in contrast to DEX, CRF-R 1 mRNA levels returned almost to control levels after 24 h. These resu lts indicate that the ability of CRF, AVP, and glucocorticoids to modu late the responses of corticotropes to CRF may be due in part to the a ctions of these agents on CRF-R1 mRNA accumulation.