July 1989

Augmented Pituitary Corticotropin Response to a Threshold Dosage of Human Corticotropin-Releasing Hormone in Depressives Pretreated With Metyrapone

Author Affiliations

From the Department of Psychiatry, Veterans Administration Medical Center, Albuquerque, NM (Drs Lisansky and Hochla and Ms Zownir-Brazis); the Departments of Psychiatry (Drs Lisansky and Strassman and Ms Zownir-Brazis), Endocrinology (Dr Peake), Mathematics and Statistics (Dr Qualls), and Physiology (Dr Britton), the University of New Mexico School of Medicine, Albuquerque; the Department of Endocrinology, University of Utah School of Medicine, Salt Lake City (Dr Meikle); the Department of Psychiatry, Emory University School of Medicine, Atlanta, Ga (Dr Risch); and the Departments of Psychiatry, University of Bologna, Italy, and the University of Buffalo (NY) School of Medicine (Dr Fava). Dr Britton is now with the Department of Pharmacology and Molecular Biology, University of Health Sciences, Chicago (Ill) Medical School.

Arch Gen Psychiatry. 1989;46(7):641-649. doi:10.1001/archpsyc.1989.01810070067011

• We studied pituitary corticotropin response to exogenous corticotropin-releasing hormone infusion and attempted to control for the confounding effect of variable serum cortisol levels between depressed and control subjects. If metyrapone was given during the time of day when hypothalamic pituitary adrenal activity was otherwise low, the relative increase in the corticotropin concentration was small. Pituitary response to exogenous corticotropin-releasing hormone can be defined under conditions in which the amount of glucocorticoid-mediated negative feedback present at the level of the pituitary gland is equal in all subjects. When the ambient cortisol level was equalized (and suppressed) in all subjects at the time of study with a threshold dosage of corticotropin-releasing hormone, we found an augmented response to corticotropin-releasing hormone in depressives. This raises the possibility that either increased pituitary sensitivity to corticotropin-releasing hormone or an increased intracellular pool of corticotropin is available for release in subjects with major depressive illness.