Corticotropin-releasing hormone, proopiomelanocortin, and glucocorticoid receptor gene expression in adrenocorticotropin-producing tumors in vitro.
To differentiate between ectopic ACTH syndrome and Cushing's disease, gene expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and glucocorticoid receptor was examined in 10 pituitary adenomas (Cushing's disease) and in 10 ectopic ACTH-producing tumors. CRH increased plasma ACTH levels in all patients with Cushing's disease and in five patients with ectopic ACTH syndrome whose tumors contained CRH and CRH mRNA. In five CRH nonresponders, CRH was not detected in tumors that contained no CRH mRNA or that contained only long-size CRH mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all patients with Cushing's disease and in three patients with ectopic ACTH-producing bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRH 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 CRH mRNA and PMA-induced POMC gene expression. In addition, there are two ectopic ACTH syndrome subtypes: tumors containing ACTH with CRH (CRH responder) and tumors without CRH. Dex decreases ACTH release and POMC mRNA levels in some bronchial carcinoids. Therefore, CRH and Dex tests have limited usefulness in differentiating between Cushing's disease and ectopic ACTH syndrome.
Suda
T
T
Department of Medicine, Tokyo Women's Medical College, Japan.
Tozawa
F
F
Dobashi
I
I
Horiba
N
N
Ohmori
N
N
Yamakado
M
M
Yamada
M
M
Demura
H
H
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000236:Adenoma / Q000378:metabolism* / Q000601:surgery; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D001127:Arginine Vasopressin / Q000494:pharmacology; D001943:Breast Neoplasms / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D003480:Cushing Syndrome / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000097:blood; D005260:Female; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism; D008297:Male; D008797:Metyrapone; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000601:surgery; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D001127:Arginine Vasopressin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011333:Pro-Opiomelanocortin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone; D008797:Metyrapone