Continuous adrenocorticotropin administration in hypopituitarism produces asynchronous increases of deoxycorticosterone and 11-deoxycortisol relative to other reduced zona fasciculata steroids.
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-450(21) appeared less influenced by lack of ACTH than mitochondrial cytochrome P-450(11 beta-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-450(21) and P-450(17 alpha) to maintain DOC and S levels contrasts the reduced and delayed responses of steroids dependent on mitochondrial cytochrome P-450(11 beta-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-450(21) and P-450(17 alpha) in a setting of reduced ACTH-stimulated factors.
Kater
C E
CE
San Francisco General Hospital Medical Center, University of California 94110.
Irony
I
I
Biglieri
E G
EG
Faiçal
S
S
D015065:17-Hydroxycorticosteroids / Q000097:blood*; D000305:Adrenal Cortex Hormones / Q000097:blood / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000172:deficiency*; D000328:Adult; D003350:Cortodoxone / Q000097:blood*; D003366:Cosyntropin / Q000627:therapeutic use; D003900:Desoxycorticosterone / Q000097:blood / Q000378:metabolism*; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007018:Hypopituitarism / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000097:blood* / Q000150:complications; D012016:Reference Values; D015383:Zona Fasciculata / Q000503:physiopathology*
D015065:17-Hydroxycorticosteroids; D000305:Adrenal Cortex Hormones; D003366:Cosyntropin; D003900:Desoxycorticosterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003350:Cortodoxone