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Continuous Adrenocorticotropin Administration in Hypopituitarism Produces Asynchronous Increases of Deoxycorticosterone and 11-Deoxycortisol Relative to Other Reduced Zona Fasciculata Steroids^*

San Francisco General Hospital Medical Center and the General Clinical Research Center, University of California San Francisco, California 94110
Division of Endocrinology, Escola Paulista de Medicina Sao Paulo, SP Brasil

Address requests for reprints to: Dr. Edward G. Biglieri, University of California, Clinical Study Center, Building 100, San Francisco General Hospital, San Francisco, California 94110.

Short term suppression of ACTH by dexamethasone effects limited reduction in plasma deoxycorticosterone (DOC) while cortisol levels are almost completely suppressed in normal control subjects. The zona fasciculata (ZF) microsomal cytochrome P-450₂₁ appeared less influenced by lack of ACTH than mitochondrial cytochrome P-450_11β–18. Eleven patients with hypopituitarism were studied to quantitate basal ZF microsomal and mitochondrial derived steroids and their acute and extended responses to ACTH. Basal levels of 11-deoxycortisol (S) and DOC were modestly reduced (70% and 53%, respectively), while other ZF steroids were almost completely absent. Acute and prolonged ACTH treatment amplified the discrepancy in both plasma levels and production rates. DOC and S demonstrated prompt and sustained increases similar to those in normal controls, while cortisol, 18-hydroxydeoxycorticosterone, and corticosterone showed a slow subnormal recovery of steroid production. The preservation of microsomal cytochrome P-450₂₁ and P-450₁₇ to maintain DOC and S levels contrasts the reduced and delayed responses of steroids dependent on mitochondrial cytochrome P-450_11β–18, cortisol, corticosterone, and 18-hydroxydeoxycorticosterone. A greater effect of ACTH deficiency on mitochondrial over microsomal cytochrome P-450 activity is demonstrated, and in addition, the possibility is raised that other non-ACTH regulators sustain microsomal cytochrome P-450₂₁ and P-450₁₇ in a setting of reduced ACTH-stimulated factors.

^* This work was supported in part by USPHS Grant DK-06415 from the NIAMDD and HL-11046 from the NHLBI. The studies were carried out in part in the General Clinic Research Center at San Francisco General Hospital Medical Center (MOl-RR-00083), with support by the Division of Research Resources, NIH (Bethesda, MD).

Received January 9, 1990.