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Mutation and Expression Analysis of Corticotropin-Releasing Factor 1 Receptor in Adrenocorticotropin-Secreting Pituitary Adenomas¹

Department of Endocrinology and Metabolism, Magdeburg University Hospital (K.D.D., H.L.), 39120 Magdeburg; Institute for Neurobiology (E.D.G.), 39118 Magdeburg; and Department of Neurosurgery, University Hospital Eppendorf (D.K.L.), 20246 Hamburg, Germany

Address all correspondence and requests for reprints to: Klaus Dieterich, Department of Endocrinology and Metabolism, Magdeburg University Hospital, Leipzigerstrasse 44, 39120 Magdeburg, Germany. E-mail: dieteric{at}hermes.med.uni-magdeburg.de

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.

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