Modulation of CRF-R1 mRNA in rat anterior pituitary by dexamethasone: correlation with POMC mRNA.

Glucocorticoids have been shown to decrease CRF receptor binding in the anterior pituitary. To determine whether glucocorticoids or CRF peptide modulate CRF-R1 gene expression, CRF-R1 mRNA levels in rat pituitary and brain were measured after administration of a synthetic glucocorticoid, dexamethasone (DEX) or rat/human CRF (r/hCRF), using a sensitive solution hybridization RNase protection assay. DEX (400 micrograms/day) or r/hCRF (100 micrograms/kg/day) was administered twice daily for 5 days to male rats. DEX treatment caused a significant decrease in CRF-R1 mRNA levels in the anterior pituitary. Also, a significant positive correlation was found between CRF-R1 and POMC mRNA levels in the anterior pituitary of the individual animals: levels of both mRNAs were reduced by DEX. However, r/hCRF treatment had no significant effect on CRF-R1 mRNA levels in the anterior pituitary. In extrahypothalamic brain regions, mRNA levels of CRF-R1 did not change following either DEX or r/hCRF administration. Our data suggest that in addition to POMC and CRF genes, CRF-R1 gene may also be subject to negative feedback control by glucocorticoids.