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Effects of Cyproheptadine, Reserpine, and Synthetic Corticotropin-Releasing Factor on Pituitary Glands from Patients with Cushing's Disease^*

Department of Medicine, Tokyo Women's Medical College, Tokyo, Japan 162; and The Second Department of Medicine, Tohoku University School of Medicine (T.M., A.S.), Sendai, Japan

Address requests for reprints to: Toshihiro Suda, M.D., Department of Medicine, Tokyo Women's Medical College, 10-Kawada-Cho, Shinjuku- Ku, Tokyo, Japan 162.

Direct effects of cyproheptadine, reserpine, synthetic ovine corticotropin-releasing factor (CRF), dexamethasone, and lysine-8-vasopressin (LVP) on the secretion of immunoreactive ACTH and β-endorphin from the adenoma and the nonadenomatous tissue of patients with Cushing's disease were examined using a supervision system. Cyproheptadine and reserpine (10^–9–10^–7 M of each) suppressed immunoreactive ACTH and β-endorphin secretion from both tissues. CRF (10^–10–10^–7 M) stimulated the secretion of both peptides from the nonadenomatous tissue, but only a high dose of CRF could stimulate the secretion of these peptides from some adenomas. Such CRF-induced secretion was partially suppressed by dexamethasone. LVP (10^–9–10^–7 M) stimulated peptide secretion from both types of tissue. These results suggest direct inhibitory effects of cyproheptadine and reserpine on the secretion of these peptides from the pituitary of patients with Cushing's disease, a different stimulatory mechanism of LVP from that of CRF in these tissues, and low sensitivity of the adenoma to CRF. (J Clin Endocrinol Metab 56:1094,1983)

^* This work was supported in part by a research grant from the Japanese Ministry of Education, Science, and Culture and a research grant for intractable disease from the Japanese Ministry of Health and Welfare.

Received July 30, 1982.

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