Mutation and expression analysis of corticotropin-releasing factor 1 receptor in adrenocorticotropin-secreting pituitary adenomas

The present study was designed to investigate a possible role of CRF1 receptors (CRF1-R) in the pathogenesis of Cushing's disease. ACTH-secreting pituitary adenomas and nonsecreting pituitary adenomas have been analyzed for mutations in the CRF1-R gene by PCR and sequencing and been compared with the sequences of normal anterior pituitaries. No mutations affecting the CRF1-R protein have been found in all tumors analyzed. However, we found a significant overexpression of the CRF1-R messenger RNA in ACTH-secreting pituitary adenomas vs inactive adenomas and normal pituitaries. We conclude that mutations of the CRF1-R are unlikely to be involved in Cushing's disease. We suggest that the overexpression of the CRF1-R messenger RNA may be related to a disturbed receptor regulation in ACTH-secreting pituitary adenomas.