[Synthesis and release of CRF and ACTH in ectopic CRF/ACTH-producing tumors].

Abstract

To differentiate between ectopic ACTH syndrome and Cushing's disease, we examined the gene expression of CRF, POMC and glucocorticoid receptor in pituitary adenomas and in ectopic ACTH-producing tumors. CRF increased plasma ACTH levels in all patients with Cushing's disease and in some patients with ectopic ACTH syndrome whose tumors contained CRF and CRF mRNA. In CRF non-responders, no CRF was detected in tumors that contained no CRF mRNA or contained only long-size CRF mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all patients with Cushing's disease and in the patients with ectopic ACTH-producing bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRF increased and Dex decreased ACTH release and POMC mRNA levels in pituitary adenoma and bronchial carcinoid cells. PMA increased POMC mRNA levels only in carcinoid cells. These results reveal characteristics of ectopic ACTH-producing tumors: long-size CRF mRNA, PMA-induced POMC gene expression, two ectopic ACTH syndrome subtypes (tumors containing ACTH with CRF and tumors without CRF), and Dex-induced decrease in ACTH release and POMC mRNA levels in some bronchial carcinoid.